A simple synthesis of polyfunctionalized 4-aminopyrazolidin-3-ones as 'aza-deoxa' analogs of D-cycloserine

Article abstract of DOI:10.1002/hlca.201300169

A simple five-step synthesis of fully substituted (4RS,5RS)-4- aminopyrazolidin-3-ones as analogs of D-cycloserine was developed. It comprises a two-step preparation of 5-substituted (4RS,5RS)-4-(benzyloxycarbonylamino) pyrazolidin-3-ones, reductive alkyl

Full text of DOI:10.1002/hlca.201300169

Helvetica Chimica Acta – Vol. 97 (2014)
245
A Simple Synthesis of Polyfunctionalized 4-Aminopyrazolidin-3-ones as ꢀAza-
deoxaꢁ Analogs of d-Cycloserine
a
a
a
b
a
ˇ
by Ana Novak ), Matej Stefanicˇ ), Urosˇ Grosˇelj ), Martina Hrast ), Marta Kasunicˇ ), Stanislav
Gobecb), Branko Stanovnika)c), and Jurij Svete*a)c)
a
ˇ
ˇ
) Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, SI-1000
Ljubljana (phone: þ 386-1-2419254; fax: þ 386-1-2419220; e-mail: jurij.svete@fkkt.uni-lj.si)
b
ˇ
ˇ
) Faculty of Pharmacy, University of Ljubljana, Askerceva 7, SI-1000 Ljubljana
c) Centre of Excellence EN-FIST, Trg osvobodilne fronte 13, SI-1000 Ljubljana
A simple five-step synthesis of fully substituted (4RS,5RS)-4-aminopyrazolidin-3-ones as analogs of
d-cycloserine was developed. It comprises a two-step preparation of 5-substituted (4RS,5RS)-4-
(benzyloxycarbonylamino)pyrazolidin-3-ones, reductive alkylation at N(1), alkylation of the amidic
N(2) with alkyl halides, and simultaneous hydrogenolytic deprotection/reductive alkylation of the
primary NH2 group. The synthesis enables an easy stepwise functionalization of the pyrazolidin-3-one
core with only two types of common reagents, aldehydes (or ketones) and alkyl halides. The structures of
products were elucidated by NMR spectroscopy and X-ray diffraction.
1. Introduction. – As cyclic analogs of 3-hydrazinopropanoic acid, pyrazolidin-3-
ones are easily available by treatment of a,b-unsaturated carboxylic acid derivatives
with NH2NH2 · H2O [1 – 4]. The importance of pyrazolidin-3-one derivatives grew
significantly during the last decades due to their synthetic applicability and biological
activity. The most representative examples of important pyrazolidin-3-ones are
phenidone (1) as photographic developer [5] and COX-inhibitor [6], and Eli Lillyꢀs
antibiotics (2) [7] (Fig. 1). Recent applications of pyrazolidin-3-ones include their use
as templates in enantioselective DielsꢀAlder [8][9], Michael [10][11], and ꢁclickꢀ
reactions [12 – 14].
Fig. 1. Examples of important pyrazolidin-3-ones 1 and 2, and 4-aminopyrazolidinones, structural analogs
of (R)-4-aminoisoxazolidin-3-one (d-cycloserine; 3)
ꢂ 2014 Verlag Helvetica Chimica Acta AG, Zꢃrich

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Helvetica Chimica Acta – Vol. 97 (2014)
d-Cycloserine (3; Fig. 1), an antibiotic effective against Mycobacterium tuber-
culosis, is applied for treatment of tuberculosis as a second-line drug, due to its adverse
effects [15][16]. Recently, d-cycloserine (3) has also been used for cognitive behavioral
therapy for anxiety disorders [17], and for treatment of behavioral and neuro-
inflammatory disorders in Parkinsonꢀs disease [18]. Therefore, development of simple
and efficient synthetic methods for preparation of novel structural analogs as well as
synthesis of libraries of novel 4-aminopyrazolidin-3-one derivatives for biological
screening (and other applications) seems justified.
In the last two decades, part of our research interest has also been directed to the
chemistry of pyrazolidinones with focus on 1,3-dipolar cycloadditions of (1Z,4R,5R)-4-
(benzoylamino)-1-benzylidene-3-oxopyrazolidin-1-azomethine imines to various dipo-
larophiles [4][13]. Within this context, reductive alkylation of (4R,5R)-4-(benzoyl-
amino)-3-oxo-5-phenylpyrazolidine has also been reported [19]. Recently, we reported
the synthesis of (4RS,5RS)-4-{[(benzyloxy)carbonyl]amino}-5-phenylpyrazolidin-3-
one (5f) from methyl 2-{[(benzyloxy)carbonyl]amino}-2-(dimethoxyphosphoryl)ace-
tate (4b) via the corresponding N-Cbz-a,b-dehydro-b-phenylalanine ester 7f and
transformations of 5f into the hydantoin derivative [20]. The availability of N-
deprotectable 4-aminopyrazolidinones 5 and their structural analogy with (R)-4-
aminoisoxazolidin-3-one (d-cycloserine; 3) prompted us to extend this study towards
the synthesis of ꢁaza-deoxaꢀ analogs of 3 (Fig. 1) with the ring O-atom, O(1), replaced
by a N-atom, and with different alkyl substituents at C(5), N(1), N(2), and 4-NH2. We
herein report a simple five-step synthetic protocol for the synthesis of polyfunction-
alized 4-amino-3-pyrazolidinones 5, 10, and 12 – 19.
2. Results and Discussion. – The 5-unsubstituted pyrazolidinone 5a [21] was
obtained by heating methyl N-[(benzyloxy)carbonyl]-O-tosyl-l-serinate (4a) with
excess NH2NH2 · H2O in MeOH, as described for the synthesis of the Boc analog of 5a
[22]. Next, 3-substituted methyl 2-{[(benzyloxy)carbonyl]amino}prop-2-enoates 7b –
7k were prepared by WittigꢀHorner condensation of 4b with aldehydes and ketones
6b – 6k following a slightly modified procedure of Schmidt et al. [23]. As in previously
reported successful examples [4][20][24], 7b – 7j were then treated with excess
NH2NH2 · H2O in an alcohol at room temperature or at reflux to afford the
corresponding pyrazolidin-3-ones 5b – 5j, respectively, in yields between 23 and
100% (Scheme 1 and Table 1).
For further transformations, the representative pyrazolidinones 5a – 5d, 5f, and 5g
were used. Acid-catalyzed treatment of 5 with acetone (6d) and aromatic aldehydes 6f
and 6k – 6m in MeOH gave the corresponding azomethine imines 9a – 9k in yields in the
range of 31 – 99% yield (Scheme 2). The deuterated compound 9k was first obtained
unintentionally. After recording the NMR spectra of 5g in (D6)acetone (6m), the
solution was left to stand at room temperature for several days to give 9k as an
insoluble precipitate. In the repeated experiment, 5g was treated with excess 6m to
furnish 9k in 75% yield. Reduction of 9c with NaBH4 in MeOH at room temperature
afforded the N(1)-benzyl derivative 10e in 93% yield (Path A). The additional N(1)-
alkyl derivatives 10 were prepared by an one-pot procedure via in situ formation of
azomethine imines 9, followed by subsequent reduction with NaBH4. In this manner, a
series of ten N(1)-alkylated 4-{[(benzyloxy)carbonyl]amino}pyrazolidin-3-ones 10

Helvetica Chimica Acta – Vol. 97 (2014)
247
Scheme 1
Table 1. Yields of Compounds 5a – 5j
Compound
R1
R2
Yield [%]a)
5a
5b
5c
5d
5e
5f
5g
5h
5i
H
H
H
H
Me
62
45
83 [24]
69
23
85 [20]
44
100
43
49
Pr
iPr
Me
ꢀ(CH2)5ꢀ
Ph
H
H
H
H
H
3-NO2ꢀC6H4
4-NO2ꢀC6H4
4-ClꢀC6H4
2-HOꢀC6H4
5j
a) Yields of the isolated products.
were obtained (yields, 21 – 95%; Path B). SN2-Type alkylation at the amidic N(2)-atom
was achieved with alkyl halides 11a – 11d in DMF in the presence of K2CO3 at room
temperature to furnish the fully substituted 4-aminopyrazolidin-3-ones 12 (yields, 45 –
97%; Scheme 2 and Table 2).
Finally, transformations of the [(benzyloxy)carbonyl]amino group at C(4) were
studied. Hydrogenolytic deprotection of the 4-amino function in the Cbz-protected
intermediates 5c, 10d, 10e, 12e, and 12h gave the free amines 13, 14a, 14b, 15a, and 15b,
respectively, in almost quantitative yields (Scheme 3). When hydrogenolytic depro-
tection of the 1,5-disubstituted 4-{[(benzyloxy)carbonyl]amino}pyrazolidin-3-ones 10a

248
Helvetica Chimica Acta – Vol. 97 (2014)
Scheme 2
and 10d was carried out in the presence of 6, the 4-(alkylamino)pyrazolidin-3-ones
16a – 16i were obtained (yields, 75 – 100%). Somewhat surprisingly, acylations of the
1,2-unsubstituted (4RS,5RS)-4-amino-5-isopropylpyrazolidin-3-one 13 with acid chlor-
ides or with carboxylic acids in the presence of activating reagents, such as 2-ethoxy-1-
(ethoxycarbonyl)-1,2-dihydroquinoline (EEDQ) and 1,1’-carbonyldiimidazole (CDI),
did not give the desired carboxamides. The only successful N-acylation of 13 was the
reaction with [1,1’-biphenyl]-4-carboxylic acid (20a) in the presence of bis(pentafluoro-
phenyl) carbonate (BPC) in DMF, which afforded the corresponding N-acyl derivative
17 in 10% yield. Though surprising, the difficult acylation of the NH2 group could be the
result of the highly polar character of 13 as a cyclic a-amino hydrazide containing three
different amino groups. On the other hand, acylation of the 1-substituted and, hence,
less polar (4RS,5RS)-4-amino-1-benzyl-5-isopropylpyrazolidin-3-ones 14a and 15a with
2-phenylacetic acid (20b) and EEDQ in CH2Cl2 proceeded smoothly to furnish the
corresponding carboxamides 18 and 19 in 83 and 82% yield, respectively (Scheme 3 and
Table 3).
The structures of all novel compounds were determined by spectroscopic methods
1
(IR, H- and 13C-NMR, and HR-MS) and by elemental analyses for C, H, and N.
Physical and spectroscopic data of known compounds 5a [21]; 5c, 9c, 9d [24]; and 9h
and 9j [20] were in agreement with those in the literature. Compounds 5i, 5j, 7i – 7k, 9k,

Helvetica Chimica Acta – Vol. 97 (2014)
Table 2. Yields of Compounds 9, 10, and 12
249
Compound
R1
R2
R3
R4
Yield [%]
9a
9b
9c
9d
9e
9f
9g
9h
9i
H
H
H
H
H
Me
Me
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
Benzylidene
Benzylidene
Benzylidene
2,6-Dichlorobenzylidene
Benzylidene
2,6-Dichlorobenzylidene
Isopropylidene
Benzylidene
–
–
–
–
–
31
58
96 [24]
99 [24]
77
60
86
81 [20]
79
74 [20]
75
90a)
21a)
48a)
92a)
56a), 93b)
53a)
63a)
78a)
21a)
95
Pr
iPr
iPr
Me
Me
Ph
Ph
Ph
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
Me
3,4,5-Trimethoxybenzylidene
2,6-Dichlorobenzylidene
(D6)Isopropylidene
9j
9k
Ph
3-NO2ꢀC6H4
10a
10b
10c
10d
10e
10f
10g
10h
10i
10j
12a
12b
12c
12d
12e
12f
12g
12h
H
iPr
Bu
iBu
iPr
Bn
Bn
Bu
iBu
iPr
Bn
iPr
iPr
iPr
iPr
Bn
Bn
Bn
Bn
iPr
iPr
iPr
iPr
Me
Ph
Ph
Ph
Ph
iPr
61
45
76
53
70
73
97
50
iPr
Bn
iPr
CH2COOEt
CH2COOtBu
Me
iPr
iPr
iPr
Bn
iPr
CH2COOEt
Me
Ph
a) Obtained by a one-pot procedure from 5. b) Obtained by reduction of 9c.
10c, 10h, 12d, 12h, 14a, 14b, 15a, 15b, 16a – 16i, and 17 were not obtained in analytically
pure form. Their identities were confirmed by 13C-NMR and HR-MS analyses.
The spectroscopic data of the pyrazolidinones 5, 10, and 12 – 19, and azomethine
imines 9 were in agreement with those in the literature reported for closely related
compounds [4][19][20][24]. In solution, pyrazolidinone derivatives 5, 9, 10, and 12 – 19
can equilibrate between the two envelope conformers A and C via the planar
1
conformer B (Fig. 2). The conformations in solution were established by H-NMR
spectroscopy on the basis of the magnitude of the vicinal coupling constants, 3J(4,5) and
3
3J(1,5). According to the coupling constants 3J(1,5) ꢁ J(4,5) ꢁ 11, the 4,5-disubstituted
compounds 5, 13, and 17 occur as envelope conformers A with pseudoaxial HꢀN(1),
HꢀC(4), and HꢀC(5) (q ca. 1808). In contrast, small vicinal coupling constants,
3J(4,5) ꢁ 3, in 1,2,4,5-tetrasubstituted pyrazolidinones 12, 14 – 16, 18, and 19 were in
agreement with conformer C, where HꢀC(4) and HꢀC(5) were pseudoequatorial
(q~1008). The conformation of 1,4,5-trisubstituted compounds 10 was dependent on
the substituent at C(5): 10g – 10j with a Ph substituent adopted conformation A with

250
Helvetica Chimica Acta – Vol. 97 (2014)
Scheme 3
3
pseudoaxial HꢀC(4) and HꢀC(5) (3J(4,5) ꢁ 11 Hz), while J(4,5) ꢁ 7 in 5-isopropyl-
pyrazolidinones 10b – 10e was in agreement with the flat conformer B (q ca. 1208).
Similarly, 3J(4,5) ꢁ 5, in dipoles 9 also supported the planar conformer B (Fig. 2).
The structures of compounds 9k, 10f, and 18 were determined by X-ray
crystallography (Figs. 3 – 5). The conformations of compounds 9k, 10f, and 18 in the
solid state were in agreement with the conformations in solution determined by NMR
spectroscopy.
Most of the synthesized compounds were also tested for their inhibitory activities
on two bacterial peptidoglycan biosynthesis enzymes, MurD ligase (MurD) and d-
alanine:d-alanine ligase (DdlB) [25]. The Malachite green assay [26], which detects
the orthophosphate generated during enzymatic reactions, was used. Unfortunately,
none of the tested compounds inhibited these two enzymes.
3. Conclusions. – In conclusion, a simple five-step method for the synthesis of
polyfunctionalized 4-aminopyrazolidin-3-ones from a-(phosphoryl)glycine ester 4b
was developed. The advantage of this method is its simplicity, which is reflected in a

Helvetica Chimica Acta – Vol. 97 (2014)
Table 3. Yields of Compounds 13 – 19
251
Compound
R1
R2
R3
R4
R5
Yield [%]
13
iPr
iPr
iPr
iPr
Ph
H
iPr
iPr
iPr
iPr
iPr
iPr
iPr
iPr
–
H
H
H
H
H
H
H
H
H
H
H
H
H
H
–
H
H
H
H
Me
Me
–
–
–
–
–
–
–
–
–
H
H
Me
–
–
–
–
–
iPr
Bu
iPr
100
100
90
97
94
100
94
100
100
96
75
99
100
100
10
14a
14b
15a
15b
16a
16b
16c
16d
16e
16f
16g
16h
16i
17
iPr
Bn
Bn
Bn
iPr
iPr
iPr
iPr
iPr
iPr
iPr
iPr
iPr
H
Cyclohexyl
Pr
Pentan-2-yl
Cyclopentyl
Cycloheptyl
(Tetrahydrofuran-3-yl)methyl
[1,1’-Biphenyl]-4-carbonyl
2-Phenylacetyl
2-Phenylacetyl
18
19
–
–
–
–
iPr
Bn
83
82
Fig. 2. Conformations of 4-aminopyrazolidin-3-one derivatives 5, 9, 10, and 12 – 19 in solution
small number of required synthetic steps and building blocks (or reagents). In total, the
title compounds are built up in two-to-five steps from phosphorylglycinate 4b,
NH2NH2 · H2O, aldehydes or ketones 6, and alkyl halides 11. The substitution pattern at
N(1), C(5) and 4-NH2 is controlled by the carbonyl compound 6, and the substituent at
N(2) by the alkyl halide 11. In summary, this method enables an easy and diverse
stepwise functionalization of 4-aminopyrazolidin-3-ones, therefore, it could also be

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Helvetica Chimica Acta – Vol. 97 (2014)
Fig. 3. The molecular structure of 9k, showing the atom labelling. The displacement ellipsoids are drawn
with 30% probability, and the H-atoms are shown as small spheres of arbitrary radii.
Fig. 4. The molecular structure of 10f, showing the atom labelling. The displacement ellipsoids are drawn
with 30% probability, and the H-atoms are indicated as small spheres of arbitrary radii.

Helvetica Chimica Acta – Vol. 97 (2014)
253
Fig. 5. The molecular structure of 18, showing the atom labelling. The displacement ellipsoids are drawn
with 30% probability, and the H-atoms are indicated as small spheres of arbitrary radii.
useful for the preparation of libraries of diversely functionalized pyrazolidin-3-ones in
search for novel bioactive compounds and other applications.
The financial support from the Slovenian Research Agency through grants P1-0179 and L1-4039 is
gratefully acknowledged. The authors thank Dr. Didier Blanot for providing MurD, and Prof. Ian Chopra
for providing DdlB.
Experimental Part
1. General. Catalytic hydrogenations: Parr Pressure Reaction Hydrogenation Apparatus 500 ml
3916EF. Flash column chromatography (FC) and column chromatography (CC): silica gel (SiO2; Fluka,
silica gel 60; particle size, 0.035 – 0.070 mm). TLC: Aluminium sheets, SiO2 60 F254 (Fluka). Medium-
pressure liquid chromatography (MPLC): Bꢀchi Sepacore Flash Chromatography System (Bꢀchi
Fraction Collector C-660, Bꢀchi Pump Module C-605, Bꢀchi Control Unit C-620) on SiO2 (Merck,
LiChroprep ꢄ Si 60; particle size, 0.015 – 0.025 mm); column dimensions, 36 ꢂ 460 mm; backpressure, 10
bar; detection, UV (254 nm). M.p.: Kofler micro hot stage and Stanford Research Systems MPA100
OptiMelt automated melting-point system; uncorrected. IR Spectra: PerkinElmer Spectrum BX FT-IR
.
spectrophotometer; ˜n in cmꢀ1 1H- and 13C-NMR spectra: Bruker Avance III UltraShield 500 plus
instrument (500 and 126 MHz, resp.) in (D6)DMSO, CDCl3, and (D6)acetone; d in ppm rel. to Me4Si as
internal standard, J in Hz. MS and HR-MS: Agilent 6224 Accurate Mass TOF LC/MS spectrometer; in
m/z. Microanalyses: PerkinElmer CHN Analyser 2400 II.
2. Starting Materials. Aldehydes and ketones 6b – 6r, alkyl halides 11a – 11d, NH2NH2 · H2O,
diazabicyclo[5.4.0]undec-7-ene (DBU), NaBH4, NaBH3CN, 2-ethoxy-1-(ethoxycarbonyl)-1,2-dihydro-
quinoline (EEDQ), bis(pentafluorophenyl) carbonate (BPC), and 10% Pd/C are commercially
available (SigmaꢀAldrich). Methyl N-[(benzyloxy)carbonyl]-O-tosyl-l-serinate (4a) [27], methyl 2-
{[(benzyloxy)carbonyl]amino}-2-(dimethoxyphosphoryl)acetate (4b) [28], 3-substituted methyl 2-
{[(benzyloxy)carbonyl]amino}acrylates 7c – 7f [23], benzyl ((3RS,4RS)-3-substituted-5-oxopyrazolidin-

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Helvetica Chimica Acta – Vol. 97 (2014)
4-yl)carbamates 5c [24] and 5f [20], and (4RS,5RS)-1-[(Z)-arylmethylidene]-4-{[(benzyloxy)carbonyl]-
amino}-3-oxo-5-substituted-pyrazolidin-1-ium-2-ides 9c, 9d [24] and 9h, 9j [20] were prepared according
to the literature procedures.
3. General Procedure for the Preparation of 3-Substituted Methyl 2-{[(Benzyloxy)carbonyl]ami-
no}acrylates 7 (GP 1). Compounds 7 were prepared according to a slightly modified literature procedure
[23]. A mixture of 4b (16.6 g, 50 mmol), CH2Cl2 (200 ml), DBU (52.5 mmol, 7.83 ml), and 61) (50 mmol)
was stirred at r.t. for 3 – 24 h. Volatile components were evaporated in vacuo, and the residue was diluted
with AcOEt (150 ml) and washed with 1m aq. NaHSO4 (2 ꢂ 70 ml). The combined org. phase was dried
(Na2SO4), filtered, and the filtrate was evaporated in vacuo to give 7.
3.1. Methyl (2E)-2-{[(Benzyloxy)carbonyl]amino}hex-2-enoate (7b) [29]. Prepared from 4b (6.6 g,
20 mmol) and 6b (1.08 ml, 20 mmol), 3 h. Yield: 5.54 g (100%). Colorless oil. ([29a]: m.p. 38.58).
Spectroscopic data were in agreement with those in the literature [29b][29c].
3.2. Methyl (2Z)-2-{[(Benzyloxy)carbonyl]amino}-3-(3-nitrophenyl)prop-2-enoate (7g). Prepared
from 4b (1.65 g, 5 mmol) and 6g (0.755 g, 5 mmol); 3 h. Yield: 0.73 g (41%). White solid. M.p. 105 – 1098.
IR (KBr): 3545, 3468, 3412, 3287, 3234, 1715, 1697, 1617, 1531, 1455, 1409, 1352, 1293, 1239, 1214, 1147,
1061, 1029, 967, 899, 834, 818, 772, 738, 696, 618. 1H-NMR (CDCl3): 3.87 (s, Me); 5.07 (s, CH2); 6.76 (br. s,
NH); 7.23 – 7.40 (m, 5 H, Ph); 7.33 (s, HꢀC(3)); 7.46 (t, J ¼ 8.0, 1 H, C6H4); 7.74 (d, J ¼ 7.6, 1 H, C6H4); 8.12
(d, J ¼ 8.1, 1 H, C6H4); 8.31 (s, 1 H, C6H4). 13C-NMR (CDCl3): 53.3; 68.1; 123.7; 124.2; 125.9; 127.2; 128.6;
128.7; 128.8; 129.5; 135.2; 135.7; 136.1; 148.4; 153.0; 165.3. ESI-MS: 357 ([M þ H]þ). HR-ESI-MS:
357.1081 ([M þ H]þ, C18H17N2O6þ ; calc. 357.1081). Anal. calc. for C18H16N2O6 (356.33): C 60.67, H 4.53, N
7.86; found: C 60.87, H 4.61, N, 7.87.
3.3. Methyl (2Z)-2-{[(Benzyloxy)carbonyl]amino}-3-(4-nitrophenyl)prop-2-enoate (7h) [30]. Pre-
pared from 4b (3.31 g, 10 mmol) and 6h (1.37 g, 9 mmol), 3 h. The crude 7h was further purified by CC
(AcOEt/hexanes 1:9). Yield: 2.1 g (58%). Yellow solid. M.p. 110 – 1148 ([6]: m.p. 124 – 1268). IR (KBr):
3258, 1733, 1698, 1641, 1597, 1520, 1508, 1490, 1455, 1438, 1346, 1311, 1287, 1273, 1240, 1209, 1189, 1146,
1071, 863, 849, 770, 748, 695, 670. 1H-NMR (CDCl3): 3.87 (s, Me); 5.06 (s, CH2); 6.78 (br. s, NH); 7.28 –
7.37 (m, 5 arom. H); 7.31 (s, HꢀC(3)); 7.55, 8.10 (2d, 1:1, J ¼ 8.7, C6H4). 13C-NMR (CDCl3): 53.3; 68.0;
123.8; 126.6; 128.7; 128.7; 128.7; 128.8; 130.0; 130.0; 135.7; 141.0; 147.4; 165.2. ESI-MS: 357 ([M þ H]þ).
HR-ESI-MS: 357.1079 ([M þ H]þ, C18H17N2O6þ ; calc. 357.1081). Anal. calc. for C18H16N2O6 (356.33): C
60.67, H 4.53, N 7.86; found: C 60.42, H 4.43, N 7.83.
3.4. Methyl (2Z)-2-{[(Benzyloxy)carbonyl]amino}-3-(4-chlorophenyl)prop-2-enoate (7i) [31]. Pre-
pared from 4b (3.31 g, 10 mmol) and 6i (1.69 g, 12 mmol); 3 h. Yield: 3.45 g (100%). Brown oil. IR
(NaCl): 3260, 3068, 3033, 2952, 2980, 1718, 1691, 1645, 1591, 1508, 1488, 1455, 1437, 1404, 1389, 1375, 1313,
1
1266, 1212, 1144, 1088, 1064, 1029, 101, 993, 962, 918, 902, 875, 849, 824, 774, 752, 698, 652. H-NMR
(CDCl3): 3.80 (s, Me); 5.09 (s, CH2); 6.54 (br. s, NH); 7.25 – 7.42 (m, Ph, C6H4); 7.29 (s, HꢀC(3)).
13C-NMR (CDCl3): 53.0; 67.8; 124.4; 127.2; 128.5; 128.5; 128.7; 128.7; 129.0; 129.6; 131.1; 131.1; 165.8;
191.1. ESI-MS: 346 ([M þ H]þ). HR-ESI-MS: 346.0845 ([M þ H]þ, C18H17ClNOþ4 ; calc. 346.0841).
3.5. Methyl (2Z)-2-{[(Benzyloxy)carbonyl]amino}-3-(2-hydroxyphenyl)prop-2-enoate (7j). Pre-
pared from 4b (6.29 g, 19 mmol) and 6j (2 ml, 19 mmol), 3 h. Yield: 5.46 g (88%). Colorless oil. IR
(NaCl): 3336, 3315, 3065, 3033, 2952, 2851, 1693, 1633, 1603, 1486, 1454, 1436, 1382, 1358, 1339, 1307, 1220,
113, 1102, 1048, 1027, 992, 945, 898, 852, 816, 752, 696, 617. 1H-NMR (CDCl3): 3.74 (s, Me); 5.10 (s, CH2);
5.23 (s, OH); 6.80 – 6.90 (m, 2 arom. H); 7.27 – 7.43 (m, 7 arom. H); 7.32 (s, HꢀC(3)). 13C-NMR (CDCl3):
52.8; 67.9; 116.8; 120.6; 128.4; 128.5; 128.7; 128.9; 130.8; 133.9; 137.2; 153.8; 158.7; 166.0. ESI-MS: 328
([M þ H]þ). HR-ESI-MS: 328.1185 ([M þ H]þ, C18H18NOþ5 ; calc. 328.1179).
3.6. Methyl (2Z)-2-{[(Benzyloxy)carbonyl]amino}-3-(3,4,5-trimethoxyphenyl)prop-2-enoate (7k).
Prepared from 4b (3.31 g, 10 mmol) and 6k (1.78 g, 9.1 mmol), 3 h. The crude 7k was purified by CC
(AcOEt/hexanes 1:9). Yield: 2.22 g (55%). White solid. M.p. 114 – 1198. IR (KBr): 3305, 2997, 2946,
2842, 1719, 1639, 1581, 1505, 1455, 1435, 1418, 1388, 1334, 1312, 1262, 1240, 1191, 1159, 1128, 1053, 1001,
1
)
In the reactions of 4b with acetone 6d and cyclohexanone 6e, these two ketones were also used as
solvents (200 ml each) instead of CH2Cl2.

Helvetica Chimica Acta – Vol. 97 (2014)
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755, 698, 667. 1H-NMR (CDCl3): 3.72, 3.83, 3.87 (4s, 1:2 :1, 4 Me); 5.13 (s, CH2); 6.30 (br. s, NH); 6.78 (s,
C6H2); 7.31 (s, HꢀC(3)); 7.32 – 7.40 (m, Ph). 13C-NMR (CDCl3): 52.8; 56.0; 56.0; 61.0; 67.7; 107.2; 107.2;
123.5; 128.3; 128.5; 128.7; 129.0; 132.6; 136.0; 139.3; 153.1; 153.1; 154.1; 165.9. ESI-MS: 402 ([M þ H]þ).
HR-ESI-MS: 402.1541 ([M þ H]þ, C21H24NOþ7 ; calc. 402.1547).
4. Benzyl (4RS)-(3-Oxopyrazolidin-4-yl)carbamate (5a). This compound was prepared following a
slightly modified literature procedure for the synthesis of the t-Bu analog [22]. A mixture of 4a (4.07 g,
10 mmol), MeOH (50 ml), and NH2NH2 · H2O (1.5 ml, 30 mmol) was refluxed for 1 h. The volatile
components were evaporated in vacuo, the residue was taken up in 1m aq. NaHCO3 (30 ml), and the
product was isolated by continuous extraction with CHCl3 (100 ml). The precipitate was collected by
filtration to give 5 [1]. Yield: 1.46 g (62%). Beige solid. M.p. 151 – 1548 ([21]: 155 – 1568).
5. General Procedures for the Preparation of Pyrazolidin-3-ones 5 (GP 2). A mixture of
7
(20 mmol), alcohol (30 ml), and NH2NH2 · H2O (3 – 5 equiv.) was stirred at r.t. or at reflux for 3 – 336 h.
Workup A: General Procedure 2A (GP 2A). The precipitate was collected by filtration and washed
with the mother liquor and hexanes to give 5.
Workup B: General Procedure 2B (GP 2B). Volatile components were evaporated in vacuo, and the
residue was purified by CC (AcOEt). Fractions containing the product were combined and evaporated in
vacuo to give 5.
5.1. Benzyl [(4RS,5RS)-3-Oxo-5-propylpyrazolidin-4-yl]carbamate (5b). Prepared from 7b (4.33 g,
15.6 mmol), NH2NH2 · H2O (2.28 ml, 47 mmol), and PrOH (30 ml); r.t. for 3 h; GP 2A. Yield: 1.94 g
(45%). White solid. M.p. 178 – 1828. IR (KBr): 3440, 3327, 3207, 2959, 2932, 1718, 1695, 1661, 1639, 1541,
1456, 1420, 1364, 1297, 1279, 1257, 1241, 1168, 1064, 776, 755, 730, 696. 1H-NMR ((D6)DMSO): 0.85 (t, J ¼
7.3, Me); 1.20 – 1.41, 1.42 – 1.58 (2m, 1:1, 2 CH2); 3.15 (dt, J ¼ 6.7, 11.1, HꢀC(5)); 3.95 (dd, J ¼ 9.5, 11.1,
HꢀC(4)); 4.90 (d, J ¼ 11.4, HꢀN(1)); 5.04, 5.06 (2d, 1:1, J ¼ 12.4, CH2); 7.28 – 7.40 (m, 5 arom. H); 7.54 (d,
J ¼ 9.5, HNꢀC(4)); 9.21 (s, HꢀN(2)). 13C-NMR ((D6)DMSO): 14.0; 18.8; 32.9; 57.7; 62.8; 65.5; 127.7;
127.9; 128.4; 137.1; 156.3; 173.9. ESI-MS: 278 ([M þ H]þ). HR-ESI-MS: 278.1501 ([M þ H]þ,
C14H20N3Oþ3 ; calc. 278.1505). Anal. calc. for C14H19N3O3 · 1/5 H2O (280.92): C 59.86, H 6.96, N 14.96;
found: C 59.83, H 6.61, N 15.07.
5.2. Benzyl [(4RS)-3,3-Dimethyl-5-oxopyrazolidin-4-yl]carbamate (5d). Prepared from 7d (5.26 g,
20 mmol), NH2NH2 · H2O (2.92 ml, 60 mmol), and PrOH (30 ml); reflux for 10 h; GP 2B. Yield: 3.66 g
(69%). White solid. M.p. 122 – 1298. IR (KBr): 3293, 3216, 3067, 3036, 2974, 2937, 1728, 1688, 1680, 1545,
1
1497, 1448, 1388, 1369, 1326, 1262, 1249, 1217, 1052, 1020, 1009, 982, 881, 805, 774, 756, 699. H-NMR
((D6)DMSO): 0.91, 1.15 (2s, 1:1, 2 Me); 4.16 (d, J ¼ 9.4, HꢀC(4)); 5.06 (s, CH2); 5.07 (d, J ¼ 3.8,
HꢀN(1)); 7.29 – 7.41 (m, 5 arom. H); 7.47 (d, J ¼ 9.4, HNꢀC(4)); 9.14 (s, HꢀN(2)). 13C-NMR
((D6)DMSO): 20.3; 23.9; 30.7; 61.1; 65.7; 127.8; 127.9; 128.4; 137.0; 156.8; 174.2. ESI-MS: 264 ([M þ
H]þ). HR-ESI-MS: 264.1339 ([M þ H]þ, C13H18N3Oþ3 ; calc. 264.1348). Anal. calc. for C13H17N3O3
(263.29): C 59.30, H 6.51, N 15.96; found: C 59.50, H 6.31, N 15.74.
5.3. Benzyl [(4RS)-3-Oxo-1,2-diazaspiro[4.5]dec-4-yl]carbamate (5e). Prepared from 7e (303 mg,
1 mmol), NH2NH2 · H2O (0.146 ml, 3 mmol), and EtOH (1.5 ml), r.t. for 336 h, GP 2B. Yield: 70 mg
(23%). White solid. M.p. 160 – 1648. IR (KBr): 3297, 3230, 3066, 3066, 2936, 2850, 1728, 1682, 1544, 1448,
1386, 1264, 1243, 1217, 1098, 1080, 1050, 754, 698. 1H-NMR (CDCl3): 1.09 – 1.33 (m, CH2); 1.38 – 1.69 (m,
3 CH2); 1.75 (d, J ¼ 14.2, 1 H, CH2); 1.96 (dt, J ¼ 3.7, 13.9, 1 H, CH2); 3.91 (s, HꢀN(1)); 4.29 (d, J ¼ 6.9,
HꢀC(4)); 5.11, 5.15 (2d, 1:1, J ¼ 12.2, CH2); 5.21 (d, J ¼ 6.9, HNꢀC(4)); 6.91 (s, HꢀN(2)); 7.27 – 7.47 (m, 5
arom. H). 13C-NMR ((D6)DMSO): 21.3; 22.0; 25.6; 26.8; 35.1; 61.7; 66.6; 67.6; 128.4; 128.5; 128.8; 136.2;
157.0; 175.8. ESI-MS: 304 ([M þ H]þ). HR-ESI-MS: 304.1655 ([M þ H]þ, C16H22N3Oþ3 ; calc. 304.1656).
Anal. calc. for C16H21N3O3 (303.36): C 63.35, H 6.98, N 13.85; found: C 63.12, H 7.09, N 13.78.
5.4. Benzyl [(3RS,4RS)-3-(3-Nitrophenyl)-5-oxopyrazolidin-4-yl]carbamate (5g). Prepared from 7g
(1.78 g, 5 mmol), NH2NH2 · H2O (2.28 ml, 47 mmol), and EtOH (13 ml); r.t. for 5 h; GP 2A. Yield:
780 mg (44%). Yellow solid. M.p. 146 – 1518. IR (KBr): 3260, 1726, 1695, 1646, 1616, 1574, 1527, 1506,
1480, 1458, 1440, 1354, 1310, 1285, 1256, 1240, 1214, 1144, 1088, 1064, 998, 929, 865, 826, 773, 752, 735, 701,
670. 1H-NMR ((D6)DMSO): 4.42 (t, J ¼ 9.7, HꢀC(4)); 4.50 (t, J ¼ 10.4, HꢀC(5)); 5.03 (br. s, CH2); 5.66
(d, J ¼ 10.4, HꢀN(1)); 7.26 – 7.38 (m, 5 arom. H); 7.70 (br. t, J ¼ 7.9, 1 H, C6H4); 7.81 (br. d, J ¼ 8.6,
HNꢀC(4)); 7.70 (br. d, J ¼ 7.8, 1 H, C6H4); 8.18 – 8.24 (m, 1 H, C6H4); 8.34 (br. t, J ¼ 2.0, 1 H, C6H4); 9.62
(s, HꢀN(2)). 13C-NMR ((D6)DMSO): 58.0; 65.0; 65.7; 121.9; 123.1; 127.7; 127.9; 128.4; 130.2; 134.1; 136.8;

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139.4; 147.9; 156.2; 172.1. ESI-MS: 357 ([M þ H]þ). HR-ESI-MS: 357.12 ([M þ H]þ, C17H17N4Oþ5 ; calc.
357.1193). Anal. calc. for C17H16N4O5 (356.33): C 57.30, H 4.53, N 15.72; found: C 57.06, H 4.43, N 15.64.
5.5. Benzyl [(3RS,4RS)-3-(4-Nitrophenyl)-5-oxopyrazolidin-4-yl]carbamate (5h). Prepared from 7h
(356 mg, 1 mmol), NH2NH2 · H2O (0.146 ml, 3 mmol), and EtOH (5 ml); r.t. for 24 h; GP 2A. Yield:
356 mg (100%). Yellow solid. M.p. 184 – 1908. IR (KBr): 3478, 3411, 3340, 3234, 3183, 1719, 1697, 1606,
1521, 1456, 1348, 1288, 1242, 1181, 1148, 1108, 1052, 952, 850, 832, 748, 698, 669. 1H-NMR ((D6)DMSO):
4.39 (t, J ¼ 9.9, HꢀC(4)); 4.48 (t, J ¼ 10.7, HꢀC(5)); 5.01, 5.04 (2d, 1:1, J ¼ 12.6, CH2); 5.67 (d, J ¼ 10.7,
HꢀN(1)); 7.25 – 7.40 (m, 5 arom. H); 7.72 (d, J ¼ 8.5, 2 H, C6H4); 7.83 (d, J ¼ 9.9, HNꢀC(4)); 8.25 (d, J ¼
8.5, 2 H, C6H4); 9.7 (br. s, HꢀN(2)). 13C-NMR ((D6)DMSO): 58.1; 65.2; 65.8; 123.7; 127.8; 128.0; 128.4;
128.6; 136.8; 144.9; 147.3; 156.2; 172.0. ESI-MS: 357 ([M þ H]þ). HR-ESI-MS: 357.1195 ([M þ H]þ,
C17H17N4Oþ5 ; calc. 357.1193). Anal. calc. for C17H16N4O5 · 1/5 H2O (359.54): C 56.73, H 4.59, N 15.57;
found: C 56.56, H 4.22, N 15.51.
5.6. Benzyl [(3RS,4RS)-3-(4-Chlorophenyl)-5-oxopyrazolidin-4-yl]carbamate (5i). Prepared from 7i
(417 mg, 1.2 mmol), NH2NH2 · H2O (0.176 ml, 3.6 mmol), and MeOH (2 ml); r.t. for 24 h; GP 2A. Yield:
148 mg (43%). Pale-yellow solid. M.p. 193 – 1978. IR (KBr): 3336, 3217, 3188, 1780, 1719, 1694, 1660,
1538, 1494, 1466, 1454, 1418, 1356, 1292, 1244, 1216, 1201, 1181, 1152, 1091, 1071, 1056, 1028, 1015, 963,
917, 857, 827, 773, 732, 707, 694, 645. 1H-NMR ((D6)DMSO): 4.32 (t, J ¼ 11.1, HꢀC(5)); 4.40 (dd, J ¼ 9.0,
11.1, HꢀC(4)); 4.99, 5.05 (2d, 1:1, J ¼ 12.5, CH2); 5.44 (d, J ¼ 11.1, HꢀN(1)); 7.30 – 7.37 (m, 5 H, Ph);
7.43 – 7.48 (m, 4 H, C6H4); 7.73 (d, J ¼ 9.0, HNꢀC(4)); 9.54 (s, HꢀN(2)). 13C-NMR ((D6)DMSO): 57.7;
65.3; 65.6; 127.8; 128.3; 128.5; 129.3; 131.1; 132.7; 135.9; 136.8; 156.2; 172.6. ESI-MS: 346 ([M þ H]þ).
HR-ESI-MS: 346.0951 ([M þ H]þ, C17H17ClN3O3þ ; calc. 346.0953).
5.7. Benzyl [(3RS,4RS)-3-(2-Hydroxyphenyl)-5-oxopyrazolidin-4-yl]carbamate (5j). Prepared from
7j (4.08 g, 12.5 mmol), NH2NH2 · H2O (2.44 ml, 50 mmol), and EtOH (40 ml); r.t. for 24 h; GP 2A2).
Yield: 1.99 g (49%). White solid. M.p. 110 – 1158. IR (KBr): 3324, 2929, 1728, 1696, 1632, 1606, 1573,
1536, 1489, 1459, 1450, 1382, 1360, 1321, 1297, 1277, 1248, 1229, 1205, 1183, 1166, 1119, 1085, 1042, 1000,
992, 943, 926, 891, 852, 758, 738, 715, 696. 1H-NMR ((D6)DMSO): 4.51 (t, J ¼ 10.9, HꢀC(5)); 4.65 (br. t,
J ¼ 10.0, HꢀC(4)); 4.95, 5.00 (2d, 1:1, J ¼ 12.5, CH2); 5.23 (br. d, J ¼ 11.3, HꢀN(1)); 6.79 (t, J ¼ 7.5, 1 H,
C6H4); 6.84 (t, J ¼ 8.0, 1 H, C6H4); 6.84 (t, J ¼ 8.0, 1 H, C6H4); 7.15 (dt, J ¼ 1.7, 7.7, 1 H, C6H4); 7.27 – 7.38
(m, 5 arom. H); 7.62 (d, J ¼ 9.2, HNꢀC(4)); 9.44 (s, HꢀN(2)); 9.88 (s, OH). 13C-NMR ((D6)DMSO): 55.6,
64.1, 65.4, 115.6, 118.4, 119.0, 123.8, 127.8, 128.3, 128.3, 136.9, 137.0, 156.1, 156.3, 169.2. ESI-MS: 328
([M þ H]þ). HR-ESI-MS: 328.1285 ([M þ H]þ, C17H18N3Oþ4 ; calc. 328.1292).
6. General Procedures for the Preparation of Azomethine Imines 9 (GP 3). Compounds 9 were
prepared following a slightly modified literature procedure [20][24]. A mixture of 5 (1 mmol), MeOH
(4 ml), and 6 (1.2 mmol) was stirred at r.t. for 5 min. Then, CF3COOH (TFA, 2 drops) was added, and
the mixture was stirred at r.t. or at reflux for 1 – 24 h.
Workup A: General Procedure 3A (GP 3A). The precipitate was collected by filtration and washed
with EtOH (2 ml) and Et2O (5 ml) to give 9.
Workup B: General Procedure 3B (GP 3B). Volatile components were evaporated in vacuo, and the
residue was purified by CC (AcOEt/EtOH). Fractions containing the product were combined, and the
solvent was evaporated in vacuo to give 9.
6.1. (2Z,4RS)-2-Benzylidene-4-{[(benzyloxy)carbonyl]amino}-5-oxopyrazolidin-2-ium-1-ide (9a).
Prepared from 5a (0.118 g, 0.5 mmol), 6f (0.061 ml, 0.5 mmol), and MeOH (5 ml); r.t. for 24 h;
GP 3A. Yield: 50 mg (31%). Pale-yellow solid. M.p. 175 – 1778. IR (KBr): 3419, 3216, 3028, 2959, 1703,
1664, 1600, 1539, 1494, 1452, 1430, 1370, 1325, 1305, 1264, 1212, 1153, 1114, 1085, 1011, 1000, 936, 871, 851,
768, 729, 701, 658, 614. 1H-NMR ((D6)DMSO): 4.31 (dd, J ¼ 6.5, 13.4, HaꢀC(5)); 4.41 – 4.47 (m,
HꢀC(4)); 4.83 (dd, J ¼ 9.6, 13.4, HbꢀC(5)); 5.05 (s, CH2); 7.29 – 7.41 (m, 5 arom. H); 7.50 – 7.59 (m, 3 arom.
H); 7.73 (s, HꢀC(1’)); 7.82 (d, J ¼ 8.0, HNꢀC(4)); 8.26 – 8.35 (m, 2 arom. H); 13C-NMR ((D6)DMSO):
50.2; 61.5; 65.6; 127.8; 127.9; 128.4; 128.8; 129.6; 131.2; 131.5; 133.3; 136.9; 156.0; 181.6. ESI-MS: 324
2
)
H2O (50 ml) was added to induce precipitation.

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([M þ H]þ). HR-ESI-MS: 324.1346 ([M þ H]þ, C18H18N3Oþ3 ; calc. 324.1343). Anal. calc. for C18H17N3O3
(323.35): C 66.86, H 5.30, N 13.00; found: C 66.61, H 5.42, N 13.13.
6.2. (2Z,3RS,4RS)-2-Benzylidene-4-{[(benzyloxy)carbonyl]amino}-5-oxo-3-propylpyrazolidin-2-
ium-1-ide (9b). Prepared from 5b (0.277 g, 1 mmol), 6f (0.122 ml, 1.2 mmol), and MeOH (5 ml); reflux
for 12 h; GP 3A. Yield: 210 mg (58%). Yellow solid. M.p. 177 – 1818. IR (KBr): 3184, 3055, 2960, 2874,
1718, 1656, 1591, 1569, 1557, 1456, 1438, 1362, 1326, 1268, 1156, 1096, 1036, 1006, 758, 737, 689. 1H-NMR
((D6)DMSO): 0.93 (t, J ¼ 7.1, Me); 1.37 – 1.47 (m, 2 H, Pr); 1.84 – 1.95, 2.05 – 2.18 (2m, 1:1, 2 H, Pr); 4.12
(dd, J ¼ 4.1, 8.4, HꢀC(4)); 4.49 (dt, J ¼ 4.1, 8.5, HꢀC(5)); 5.05 (s, CH2); 7.19 – 7.40 (m, 5 arom. H); 7.54 –
7.56 (m, 3 arom. H); 7.79 (s, HꢀC(1’)); 7.89 (d, J ¼ 8.4, HNꢀC(4)); 8.34 – 8.36 (m, 2 arom. H). 13C-NMR
((D6)DMSO): 13.6; 17.4; 35.4; 55.5; 65.6; 73.4; 127.8; 127.9; 128.4; 128.7; 129.7; 131.5; 131.6; 133.2; 136.9;
155.9; 180.1. ESI-MS: 366 ([M þ H]þ). HR-ESI-MS: 366.1804 ([M þ H]þ, C21H24N3Oþ3 ; calc. 366.1818).
Anal. calc. for C21H23N3O3 · 1/6 H2O (368.43): C 68.46, H 6.38, N 11.41; found: C 69.02, H 6.34, N 11.50.
6.3. (2Z,4RS)-2-Benzylidene-4-{[(benzyloxy)carbonyl]amino}-3,3-dimethyl-5-oxopyrazolidin-2-
ium-1-ide (9e). Prepared from 5d (1.32 g, 5 mmol), 6f (0.61 ml, 6 mmol), and MeOH (25 ml); reflux
fot 3 h; GP 3A. Yield: 1.35 g (77%). Pale-yellow solid. M.p. 200 – 2048. IR (KBr): 3549, 3466, 3412, 3311,
3048, 2975, 2958, 1720, 1699, 1666, 1593, 1570, 1541, 1453, 1418, 1399, 1377, 1360, 1327, 1304, 1277, 1239,
1
1214, 1083, 1069, 1050, 984, 908, 758,3 694, 676, 648. H-NMR ((D6)DMSO): 1.42, 1.75 (2s, 1:1, 2 Me);
4.37 (d, J ¼ 8.9, HꢀC(4)); 5.07, 5.12 (2d, 1:1, J ¼ 12.6, CH2); 7.31 – 7.39 (m, 5 arom. H); 7.54 (m, 3 arom.
H); 7.83 (d, J ¼ 8.8, HNꢀC(4)); 7.87 (s, HꢀC(1’)); 8.39 (dd, J ¼ 2.9, 6.8, 2 arom. H). 13C-NMR
((D6)DMSO): 23.5; 27.0; 59.8; 65.8; 75.0; 127.8; 127.9; 128.4; 128.7; 129.9; 131.6; 131.7; 132.0; 136.9;
156.9; 178.5. ESI-MS: 352 ([M þ H]þ). HR-ESI-MS: 352.1659 ([M þ H]þ, C20H22N3Oþ3 ; calc. 352.1661).
Anal. calc. for C20H21N3O3 (351.40): C 68.36, H 6.02, N 11.96; found: C 68.08, H 5.77, N 11.75.
6.4. (2Z,4RS)-4-{[(Benzyloxy)carbonyl]amino}-2-(2,6-dichlorobenzylidene)-3,3-dimethyl-5-oxopyr-
azolidin-2-ium-1-ide (9f). Prepared from 5d (527 mg, 2 mmol), 6l (0.42 g, 2.4 mmol), and MeOH
(40 ml); reflux for 4.5 h; GP 3A. Yield: 508 mg (60%). Pale-yellow solid. M.p. 195 – 1998. IR (KBr): 3284,
3038, 2979, 2935, 1730, 1702, 1679, 1587, 1538, 1498, 1455, 1432, 1397, 1373, 1348, 1311, 1279, 1234, 1392,
1108, 1082, 1058, 1013, 930, 879, 816, 774, 734, 965. 1H-NMR (CDCl3): 1.60, 2.05 (2s, 1:1, 2 Me); 4.52 (d,
J ¼ 4.3, HꢀC(4)); 5.12, 5.16 (2d, 1:1, J ¼ 12.3, CH2); 5.53 (d, J ¼ 3.4, NH); 7.30 – 7.40 (m, 8 H, Ph, C6H3);
7.35 (s, HꢀC(1’)). 13C-NMR (CDCl3): 24.6; 27.0; 61.3; 67.5; 77.8; 127.8; 128.1; 128.2; 128.2; 128.3; 128.4;
128.4; 128.8; 132.2; 134.8; 136.1; 157.5; 179.0. ESI-MS: 420 ([M þ H]þ). HR-ESI-MS: 420.0879 ([M þ
H]þ, C20H20Cl2N3O3þ ; calc. 420.0876). Anal. calc. for C20H19Cl2N3O3 (420.29): C 57.15, H 4.56, N 10.00;
found: C 56.88, H 4.40, N 9.96.
6.5. (3RS,4RS)-4-{[(Benzyloxy)carbonyl]amino}-5-oxo-3-phenyl-2-(propan-2-ylidene)pyrazolidin-
2-ium-1-ide (9g). Prepared from 5f (0.31 g, 1 mmol), 6d (1 ml), and MeOH (4 ml); r.t. for 24 h; GP 3B,
AcOEt/EtOH 5 :1. Yield: 0.30 g (86%). White solid. M.p. 176 – 1778. IR (KBr): 3458, 3202, 3030, 2978,
2923, 1724, 1674, 1607, 1566, 1498, 1489, 1454, 1438, 1372, 1357, 1298, 1267, 1152, 1124, 1094, 1063, 1024,
778, 764, 732, 708, 694, 654. 1H-NMR ((D6)DMSO): 1.96, 2.31 (2s, 1:1, Me); 3.90 (dd, J ¼ 2.7, 8.0,
HꢀC(4)); 5.04, 5.08 (2d, 1:1, J ¼ 12.5, CH2); 5.70 (br. s, HꢀC(5)); 7.24 – 7.47 (m, 10 arom. H); 8.11 (d, J ¼
8.0, NH). 13C-NMR ((D6)DMSO): 20.8; 22.3; 62.7; 65.7; 73.5; 125.3; 127.9; 127.9; 128.4; 128.4; 129.4;
136.8; 137.7; 151.9; 156.1; 176.7. ESI-MS: 352 ([M þ H]þ). HR-ESI-MS: 352.1644 ([M þ H]þ,
C20H22N3Oþ3 ; calc. 352.1661). Anal. calc. for C20H21N3O3 · 1/4 H2O (355.90): C 67.49, H 6.09, N 11.81;
found: C 67.49, H 6.07, N 11.72.
6.6. (2Z,3RS,4RS)-4-{[(Benzyloxy)carbonyl]amino}-5-oxo-3-phenyl-2-(3,4,5-trimethoxybenzylide-
ne)pyrazolidin-2-ium-1-ide (9i). Prepared from 5f (0.31 g, 1 mmol), 6k (236 mg, 1.2 mmol), and EtOH
(4 ml); reflux for 1 h; GP 3A. Yield: 385 mg (79%). Pale-yellow solid. M.p. 159 – 1638. IR (KBr): 3411,
3027, 3007, 2970, 2940, 1715, 1662, 1595, 1504, 1456, 1427, 1375, 1334, 1272, 1249, 1159, 1128, 1041, 1002,
778, 743, 697, 643. 1H-NMR (CDCl3): 3.86, 3.91 (2s, 2 :1, 3 Me); 4.53 (br. t, J ¼ 5.4, HꢀC(4)); 5.08 (s, CH2);
5.55 (br. d, J ¼ 5.4, HꢀC(5)); 6.06 (br. s, NH); 6.75 (s, HꢀC(1’)); 7.20 – 7.54 (m, 12 H, Ph, C6H2). 13C-NMR
(CDCl3): 56.6; 60.6; 61.3; 67.4; 79.6; 106.9; 109.8; 124.0; 127.6; 128.2; 128.4; 128.7; 129.9; 136.2; 136.5;
142.3; 153.2; 153.8; 179.3; 191.3. ESI-MS: 490 ([M þ H]þ). HR-ESI-MS: 490.1969 ([M þ H]þ,
C27H28N3Oþ6 ; calc. 490.1973). Anal. calc. for C27H27N3O6 · 1/3 H2O (459.52): C 65.44 H, 5.63, N 8.48;
found: C 65.27, H 5.87, N 8.50.

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6.7. (3RS,4RS)-4-{[(Benzyloxy)carbonyl]amino}-3-(3-nitrophenyl)-5-oxo-2-[(2H6)propan-2-ylide-
ne]pyrazolidin-2-ium-1-ide (9k). A mixture of 5g (178 mg, 0.5 mmol) and (D6)acetone 6m (1 ml) was
stirred at r.t. for 24 h. The precipitate was collected by filtration to give 9k. Yield: 151 mg (75%). White
solid. M.p. 200 – 2048. 1H- and 13C-NMR spectra could not be recorded due to insolubility of the product
in various solvents including (D6)DMSO. IR (KBr): 3087, 3032, 3002, 2969, 1697, 1669, 1615, 1527, 1456,
1419, 1351, 1307, 1260, 1219, 1166, 1110, 1084, 1068, 1038, 978, 958, 923, 895, 828, 810, 781, 758, 739, 716,
701, 685, 670. ESI-MS: 403 ([M þ H]þ). HR-ESI-MS: 403.1875 ([M þ H]þ, C20H14D6N4Oþ5 ; calc.
403.188).
7. Synthesis of Benzyl [(4RS,5RS)-1-Benzyl-3-oxo-5-(propan-2-yl)pyrazolidin-4-yl]carbamate (10e).
A stirred suspension of 9c (0.744 g, 2 mmol) in MeOH (8 ml) was stirred at 08 for 10 min. Then, NaBH4
(0.115 g, 3 mmol) was added slowly (portionwise), and the mixture was stirred at 08 for 2 h and at r.t. for
2 h. H2O (30 ml) was added, and the product was extracted with CH2Cl2 (5 ꢂ 20 ml). The combined org.
phases were dried (Na2SO4), filtered, and the filtrate was evaporated in vacuo to give 10e. Yield: 0.692 g
(93%). White solid. M.p. 138 – 1428. IR (KBr): 3267, 3065, 3035, 2959, 2872, 1725, 1693, 1687, 1558, 1550,
1542, 1497, 1455, 1275, 1261, 1172, 1027, 732, 698, 669. 1H-NMR ((D6)DMSO): 0.78, 0.83 (2d, 1:1, J ¼ 6.8,
3 H, iPr); 1.66 (sept., J ¼ 6.5, 1 H, iPr); 2.78 (t, J ¼ 6.0, HꢀC(5)); 3.84, 3.92 (2d, 1:1, J ¼ 12.9, CH2); 3.95
(dd, J ¼ 6.6, 8.8, HꢀC(4)); 5.02 (s, CH2); 7.26 – 7.38 (m, 10 arom. H); 7.96 (d, J ¼ 8.7, NH); 9.63 (s,
HꢀN(2)). 13C-NMR ((D6)DMSO): 17.3; 18.3; 29.9; 53.6; 63.4; 65.6; 72.1; 127.4; 127.8; 127.9; 128.2; 128.4;
129.4; 136.8; 137.0; 155.8; 169.0. ESI-MS: 368 ([M þ H]þ). HR-ESI-MS: 368.1964 ([M þ H]þ,
C21H26N3Oþ3 ; calc. 368.1974). Anal. calc. for C21H25N3O3 (367.44): C 68.64, H 6.86, N 11.44; found: C
68.39, H 6.49, N 11.46.
8. General One-Pot Procedure for the Synthesis of 1,5-Disubstituted (4RS,5RS)-4-{[(Benzyloxy)-
carbonyl]amino}pyrazolidin-3-ones 10 (GP 4). A mixture of 5 (1 mmol), MeOH (5 ml), 6 (1.2 mmol),
and CF3COOH (2 drops) was stirred at r.t. for 10 min. Then, NaBH4 (0.046 g, 1.2 mmol) or NaBH3CN
(0.076 g, 1.2 mmol) was added, and the mixture was stirred at r.t. or under reflux for 3 – 100 h.
Workup A: General Procedure 4A (GP 4A). The precipitate was collected by filtration and washed
with Et2O (5 ml) to give 10.
Workup B: General Procedure 4B (GP 4B). Volatile components were evaporated in vacuo, and the
residue was purified by CC (AcOEt/hexanes). Fractions containing the product were combined and
evaporated in vacuo to give 10.
8.1. Benzyl [(4RS)-3-Oxo-1-(propan-2-yl)pyrazolidin-4-yl]carbamate (10a). Prepared from 5a
(3.81 g, 16 mmol), 6d (20 ml), and NaBH4 (850 mg, 22.5 mmol); r.t. for 48 h; GP 4A. Yield: 5.81 mg
(90%). Pale-yellow solid. M.p. 132 – 1358. IR (KBr): 3554, 3418, 3308, 3064, 2980, 2811, 1682, 1617, 1548,
1530, 1454, 1390, 1368, 1340, 1291, 1279, 1242, 1176, 1081, 1064, 1026, 1009, 902, 875, 845, 783, 755, 739,
697. 1H-NMR ((D6)DMSO): 0.97, 1.00 (2d, 1:1, J ¼ 6.3, Me2CH); 2.74, 2.85 (2 br. s, 1:1, CH2); 3.50 (dd,
J ¼ 10.9, 8.6, HꢀC(4)); 4.31 – 4.42 (br. m, Me2CH); 5.04 (s, CH2); 7.27 – 7.41 (m, 5 arom. H); 7.61 (d, J ¼
8.6, NH); 9.60 (s, HꢀN(2)). 13C-NMR ((D6)DMSO): 19.5; 20.2; 51.2; 53.8; 57.2; 66.0; 128.3; 128.3; 128.8;
137.4; 156.5; 171.5. ESI-MS: 278 ([M þ H]þ). HR-ESI-MS: 278.1499 ([M þ H]þ, C14H19N3Oþ3 ; calc.
278.1499). Anal. calc. for C14H19N3O3 (277.32): C 60.63, H 6.91, N 15.15; found: C 60.60, H 7.06, N 15.09.
8.2. Benzyl [(4RS,5RS)-1-Butyl-3-oxo-5-(propan-2-yl)pyrazolidin-4-yl]carbamate (10b). Prepared
from 5c (0.277 g, 1 mmol), 6b (0.108 ml, 1.2 mmol), and NaBH3CN (0.150 g, 2.4 mmol); r.t. for 100 h;
GP 4B (AcOEt/hexanes 1:1). Yield: 67 g (21%). Pale-yellow solid. M.p. 129 – 1338. IR (KBr): 3549,
3418, 3318, 3161, 3039, 2963, 2935, 2872, 1725, 1690, 1616, 1540, 1456, 1294, 1246, 1054, 777, 732, 694, 668.
1H-NMR ((D6)DMSO): 0.85, 0.90 (2d, 1:1, J ¼ 6.5, Me3CH); 0.88 (t, J ¼ 7.1, MeCH2); 1.20 – 1.49 (m,
2 CH2); 1.79 (sept., J ¼ 6.5, Me2CH); 2.55 – 2.75 (m, CH2); 2.63 (dd, J ¼ 5.3, 7.6, HꢀC(5)); 3.92 (t, J ¼ 8.3,
HꢀC(4)); 5.05 (s, CH2); 7.29 – 7.40 (m, 5 arom. H); 7.84 (d, J ¼ 8.8, HNꢀC(4)); 9.63 (s, HꢀN(2)).
13C-NMR ((D6)DMSO): 17.0; 18.2; 18.4; 20.2; 29.6; 30.6; 36.6; 54.8; 67.2; 74.6; 128.2; 128.3; 128.6; 136.2;
145.6; 156.0. ESI-MS: 334 ([M þ H]þ). HR-ESI-MS: 334.2131 ([M þ H]þ, C18H28N3Oþ3 ; calc. 334.2131).
Anal. calc. for C18H27N3O3 · 1/5 H2O (297.03): C 64.15, H 8.19, N 12.47; found: C 64.13, H 8.19, N 12.53.
8.3. Benzyl [(4RS,5RS)-1-(2-Methylpropyl)-3-oxo-5-(propan-2-yl)pyrazolidin-4-yl]carbamate
(10c). Prepared from 5c (0.277 g, 1 mmol), 6c (0.108 ml, 1.2 mmol), and NaBH3CN (0.150 g, 2.4 mmol);
r.t. for 24 h; GP 4B (AcOEt/hexanes 1:1). Yield: 160 mg (48%). Pale-yellow solid. M.p. 168 – 1728. IR
(KBr): 3465, 3412, 3314, 3154, 3036, 2963, 2933, 2877, 1726, 1684, 1615, 1543, 1469, 1458, 1389, 1295, 1286,

Helvetica Chimica Acta – Vol. 97 (2014)
259
1248, 1052, 778, 739, 730, 694. 1H-NMR ((D6)DMSO): 0.82, 0.87, 0.89, 0.91 (4d, 1:1:1:1, J ¼ 6.7, 12 H, iPr,
i
iBu); 1.72 – 1.85 (m, 2 H, iPr, Bu); 2.30 (dd, J ¼ 10.7, 11.8, 1 H, CH2); 2.48 (dd, J ¼ 4.1, 11.8, 1 H, CH2);
2.61 (dd, J ¼ 5.3, 7.9, HꢀC(5)); 3.94 (t, J ¼ 8.4, HꢀC(4)); 5.05 (s, CH2); 7.28 – 7.40 (m, 5 arom. H); 7.87 (d,
J ¼ 8.9, NH); 9.69 (s, HꢀN(2)). 13C-NMR ((D6)DMSO): 17.4; 18.4; 20.3; 20.7; 25.7; 29.6; 53.3; 65.5; 68.2;
73.2; 127.8; 127.9; 128.4; 137.0; 155.8; 168.9. ESI-MS: 334 ([M þ H]þ). HR-ESI-MS: 334.2125 ([M þ H]þ,
C18H28N3Oþ3 ; calc. 334.2131).
8.4. Benzyl [(4RS,5RS)-3-Oxo-1,5-di(propan-2-yl)pyrazolidin-4-yl]carbamate (10d). Prepared from
5c (0.554 g, 2 mmol), 6d (2 ml), and NaBH3CN (0.150 g, 2.4 mmol); r.t. for 24 h; GP 4A. Yield: 136 g
(92%). Brownish solid. M.p. 171 – 1768. IR (KBr): 3413, 3363, 2968, 3183, 3180, 3082, 3070, 3058, 3035,
2968, 2937, 2929, 2900, 2873, 1711, 1690, 1632, 1617, 1524, 1469, 1456, 1389, 1373, 1339, 1284, 1263, 1235,
1
1049, 1036, 774, 755, 748, 700, 617, 608, 600. H-NMR ((D6)DMSO): 0.86, 0.89, 0.95, 0.99 (4d, 1:1:1:1,
J ¼ 6.5, 2 Me2CH); 1.74, 2.89 (2sept., 1:1, J ¼ 6.5, 2 Me2CH); 2.82 (t, J ¼ 5.8, HꢀC(5)); 3.90 (dd, J ¼ 6.1,
8.6, HꢀC(4)); 5.03, 5.07 (2d, 1:1, J ¼ 12.7, CH2); 7.30 – 7.39 (m, 5 arom. H); 7.92 (d, J ¼ 8.6, NH); 9.56 (s,
HꢀN(2)). 13C-NMR ((D6)DMSO): 17.3; 17.4; 18.3; 20.9; 30.7; 53.5; 55.4; 65.5; 69.4; 127.7; 127.9; 128.4;
137.0; 155.8; 168.7. ESI-MS: 320 ([M þ H]þ). HR-ESI-MS: 320.1983 ([M þ H]þ, C17H26N3Oþ3 ; calc.
320.1974). Anal. calc. for C17H25N3O3 · H2O (337.41): C 60.51, H 8.07, N 12.45; found: C 60.44, H 7.61, N
12.77.
8.5. Benzyl [(4RS,5RS)-1-Benzyl-3-oxo-5-(propan-2-yl)pyrazolidin-4-yl]carbamate (10e). Prepared
from 5c (0.277 g, 1 mmol), 6f (0.122 ml, 1.2 mmol), and NaBH4 (75 mg, 1.2 mmol); r.t. for 12 h; GP 4B
(AcOEt/hexanes 3 :1). Yield: 207 mg (56%). White solid. For physical, anal., and spectroscopic data for
10e, see above.
8.6. Benzyl [(4RS)-1-Benzyl-5,5-dimethyl-3-oxopyrazolidin-4-yl]carbamate (10f). Prepared from 5d
(0.263 g, 1 mmol), 6f (0.122 ml, 1.2 mmol), and NaBH4 (38 mg, 1.2 mmol); r.t. for 24 h; GP 4B, first FC,
then MPLC (AcOEt/hexanes 3 :1). Yield: 186 mg (53%). White solid. M.p. 116 – 1208. IR (KBr): 3406,
3318, 3059, 3033, 2972, 1717, 1698, 1541, 1454, 1371, 1353, 1282, 1253, 1092, 1081, 1062, 1022, 730, 698, 668.
1H-NMR ((D6)DMSO): 1.02, 1.20 (2s, 1:1, 2 Me); 3.88 (s, CH2); 4.42 (d, J ¼ 9.3, HꢀC(4)); 5.06, 5.11 (2d,
1:1, J ¼ 12.5, CH2); 7.23 – 7.39 (m, 10 arom. H); 7.66 (d, J ¼ 9.3, HNꢀC(4)); 9.40 (s, HꢀN(2)). 13C-NMR
((D6)DMSO): 19.8; 23.5; 56.0; 59.1; 65.3; 65.7; 126.9; 127.8; 127.9; 128.1; 128.4; 128.8; 136.9; 138.2; 156.8;
171.1. ESI-MS: 354 ([M þ H]þ). HR-ESI-MS: 354.1808 ([M þ H]þ, C20H24N3Oþ3 ; calc. 354.1818). Anal.
calc. for C20H23N3O3 (353.41): C 67.97, H 6.56, N 11.89; found: C 67.96, H 6.26, N 11.85.
8.7. Benzyl [(4RS,5RS)-1-Butyl-3-oxo-5-phenylpyrazolidin-4-yl]carbamate (10g). Prepared from 5f
(311 mg, 1 mmol), 6b (0.108 ml, 1.2 mmol), and NaBH3CN (150 mg, 2.4 mmol); reflux for 3 h; GP 4B
(AcOEt/hexanes 1:1). Yield: 232 mg (63%). White solid. M.p. 136 – 1408. IR (KBr): 3450, 3335, 3063,
3036, 2950, 2869, 2843, 1713, 1688, 1533, 1497, 1468, 1455, 1381, 1358, 1312, 1253, 1078, 1050, 784, 456, 706,
697. 1H-NMR ((D6)DMSO): 0.75 (t, J ¼ 7.3, Me); 1.15, 1.26 (2tq, 1:1, J ¼ 7.4, 7.4, CH2); 1.40 (tt, J ¼ 7.2, 7.2,
CH2); 2.39 (td, J ¼ 7.3, 12.5, 1 H, CH2); 2.55 (td, J ¼ 8.1, 12.5, 1 H, CH2); 3.75 (d, J ¼ 11.4, HꢀC(5)); 4.11
(dd, J ¼ 9.0, 11.4, HꢀC(4)); 4.97, 5.00 (2d, 1:1, J ¼ 12.7, 1 H, CH2); 7.26 – 7.40 (m, 10 arom. H); 7.85 (d, J ¼
9.0, NH); 9.92 (s, HꢀN(2)). 13C-NMR ((D6)DMSO): 13.6; 19.6; 28.5; 30.7; 57.4; 65.5; 72.0; 127.6; 127.7;
127.8; 128.0; 128.4; 128.6; 136.9; 138.3; 155.9; 168.2. ESI-MS: 368 ([M þ H]þ). HR-ESI-MS: 368.1960
([M þ H]þ, C21H26N3Oþ3 ; calc. 368.1974). Anal. calc. for C21H25N3O3 (367.44): C 68.64, H 6.86, N 11.44;
found: C 68.57, H 6.95, N 11.40.
8.8. Benzyl [(4RS,5RS)-1-(2-Methylpropyl)-3-oxo-5-phenylpyrazolidin-4-yl]carbamate (10h). Pre-
pared from 5f (311 mg, 1 mmol), 6b (0.091 ml, 1.2 mmol), and NaBH3CN (150 mg, 2.4 mmol); reflux for
5 h; GP 4B (AcOEt/hexanes 1:1). Yield: 289 mg (78%). White solid. M.p. 140 – 1458. IR (KBr): 3458,
3279, 3258, 3154, 3036, 2959, 2932, 2872, 2831, 1724, 1691, 1545, 1497, 1454, 1387, 1365, 1260, 1180, 1060,
758, 735, 701. 1H-NMR ((D6)DMSO): 0.73, 0.81 (2d, 1:1, J ¼ 6.8, 2 Me); 0.95 (m, 1 H, iBu); 2.17 (dd, J ¼
i
i
10.6, 11.9, 1 H, Bu); 2.30 (dd, J ¼ 4.3, 11.9, 1 H, Bu); 3.73 (d, J ¼ 11.4, HꢀC(5)); 4.08 (dd, J ¼ 9.0, 11.4,
HꢀC(4)); 4.97, 4.99 (2d, 1:1, J ¼ 12.7, CH2); 7.26 – 7.41 (m, 10 arom. H); 7.86 (d, J ¼ 9.0, NH); 9.94 (s,
HꢀN(2)). 13C-NMR ((D6)DMSO): 20.3; 20.6; 25.4; 60.0; 65.5; 66.1; 72.2; 127.6; 127.7; 127.8; 128.2; 128.4;
128.6; 136.9; 138.2; 155.9; 168.3. ESI-MS: 368 ([M þ H]þ). HR-ESI-MS: 368.1964 ([M þ H]þ,
C21H26N3Oþ3 ; calc. 368.1974).
8.9. Benzyl [(4RS,5RS)-3-Oxo-5-phenyl-1-(propan-2-yl)pyrazolidin-4-yl]carbamate (10i). Prepared
from 5f (311 mg, 1 mmol), 6d (1 ml), and NaBH3CN (150 mg, 2.4 mmol); reflux for 24 h; GP 4A. Yield:

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74 mg (21%). White solid. M.p. 182 – 1868. IR (KBr): 3475, 3385, 3064, 3038, 2978, 1726, 1698, 1635, 1518,
1454, 1391, 1376, 1346, 1285, 1230, 1199, 1155, 1038, 752, 699, 635, 546. 1H-NMR ((D6)DMSO): 0.95, 0.96
(2d, 1:1, J ¼ 6.5, 2 Me); 2.76 (sept., J ¼ 6.5, Me2CH); 3.99 – 4.04 (m, HꢀC(4), HꢀC(5)); 5.00 (s, CH2);
7.30 – 7.41 (m, 10 arom. H); 7.88 (dd, J ¼ 8.3, NH); 9.73 (s, HꢀN(2)). 13C-NMR ((D6)DMSO): 15.6; 20.6;
53.5; 60.5; 65.5; 67.6; 127.3; 127.6; 127.8; 127.8; 128.4; 128.6; 136.9; 139.8; 155.9; 167.5. ESI-MS: 354 ([M þ
H]þ). HR-ESI-MS: 354.1817 ([M þ H]þ, C20H24N3O3þ ; calc. 354.1818). Anal. calc. for C20H23N3O3 · 1/
2 H2O (362.43): C 66.28, H 6.67, N 11.59; found: C 66.20, H 6.36, N 11.53.
8.10. Benzyl [(4RS,5RS)-1-Benzyl-3-oxo-5-phenylpyrazolidin-4-yl]carbamate (10j). Prepared from
5f (1.555 g, 5 mmol), 6f (0.610 ml, 6 mmol), and NaBH4 (0.190 g, 5 mmol); r.t. for 2 h; GP 4B (AcOEt).
Yield: 1.91 g (95%). White solid. M.p. 178 – 1828. IR (KBr): 3442, 3331, 1717, 1691, 1539, 1497, 1455, 1352,
1
1352, 1254, 1057, 756, 696. H-NMR ((D6)DMSO): 3.60, 3.89 (2d, 1:1, J ¼ 13.9, CH2); 3.93 (d, J ¼ 10.7,
HꢀC(5)); 4.16 (dd, J ¼ 9.2, 10.7, HꢀC(4)); 4.99 (s, CH2); 6.90 – 7.50 (m, 15 arom. H); 7.93 (d, J ¼ 9.2, NH);
9.86 (s, HꢀN(2)). 13C-NMR ((D6)DMSO): 59.9; 60.0; 65.5; 70.4; 127.4; 127.6; 127.6; 127.8; 128.1; 128.3;
128.4; 128.6; 129.3; 135.7; 136.9; 137.9; 156.0; 168.2. ESI-MS: 402 ([M þ H]þ). HR-ESI-MS: 402.1805
([M þ H]þ, C24H24N3Oþ3 ; calc. 402.1818). Anal. calc. for C24H23N3O3 (401.46): C 71.80, H 5.77, N 10.47;
found: C 71.60, H 5.51, N 10.72.
9. General Procedure for the Synthesis of 1,2,5-Trisubstituted (4RS,5RS)-4-{[(Benzyloxy)carbonyl]-
amino}pyrazolidin-3-ones 12 (GP 5). A mixture of 10 (1 mmol), anh. DMF (5 ml), K2CO3 (138 mg,
1 mmol), and 11 (1 – 8 mmol) was stirred under Ar for 24 – 96 h. Volatile components were evaporated in
vacuo, and the residue was purified by CC (AcOEt/hexanes). Fractions containing the product were
combined and evaporated in vacuo to give 12.
9.1. Benzyl [(3RS,4RS)-1-Methyl-5-oxo-2,3-di(propan-2-yl)pyrazolidin-4-yl]carbamate (12a). Pre-
pared from 10d (319 mg, 1 mmol) and 11a (227 ml, 3.3 mmol); 96 h; CC (AcOEt/hexanes 1:2). Yield:
204 mg (61%). Pale-yellow solid. M.p. 107 – 1118. IR (KBr): 3243, 3063, 3035, 2978, 2964, 2928, 2892,
2873, 1709, 1665, 1587, 1526, 1487, 1456, 1430, 1402, 1386, 1378, 1362, 1349, 1339, 1301, 1258, 1214, 1156,
1134, 1111, 1096, 1082, 1056, 1017, 996, 972, 960, 916, 903, 861, 837, 791, 779, 761, 737, 701, 663. 1H-NMR
((D6)DMSO): 0.88 – 0.99 (m, 3 Me); 1.09 (d, J ¼ 6.7, Me); 1.78 – 1.88 (m, Me2CH); 2.96 (br. s, HꢀC(3));
3.00 (s, MeꢀC(1)); 3.25 (sept., J ¼ 6.7, Me2CH); 4.11 (d, J ¼ 2.9, HꢀC(4)); 5.09, 5.15 (2d, 1:1, J ¼ 12.1,
CH2); 5.11 (br. s, NH, overlapped by the signal for CH2); 7.30 – 7.39 (m, 5 arom. H). 13C-NMR
((D6)DMSO): 17.1; 17.2; 18.5; 20.0; 31.4; 33.2; 52.6; 55.7; 65.5; 67.2; 128.3; 128.3; 128.6; 136.2; 156.1;
168.2. ESI-MS: 334 ([M þ H]þ). HR-ESI-MS: 334.2125 ([M þ H]þ, C18H28N3Oþ3 ; calc. 334.2125). Anal.
calc. for C18H27N3O3 (333.21): C 64.84, H 8.16, N 12.60; found: C 65.05, H 8.42, N 12.60.
9.2. Benzyl [(3RS,4RS)-1-Benzyl-5-oxo-2,3-di(propan-2-yl)pyrazolidin-4-yl]carbamate (12b). Pre-
pared from 10d (319 mg, 1 mmol) and 11b (119 ml, 1.3 mmol); 72 h; CC (AcOEt/hexanes 1:2). Yield:
182 mg (45%). Yellow solid. M.p. 112 – 1158. IR (KBr): 3235, 3090, 3066, 3036, 2976, 2958, 2890, 2874,
1699, 1662, 1521, 1496, 1448, 1385, 1369, 1346, 1325, 1303, 1264, 1218, 1167, 1160, 1128, 1117, 1098, 1084,
1058, 1046, 1019, 997, 966, 916, 902, 862, 824, 784, 752, 737, 698, 678. 1H-NMR ((D6)DMSO): 0.81, 0.69
(2d, 1:1, J ¼ 4.7, 2 Me); 0.85, 1.04 (2d, 1:1, J ¼ 6.6, 2 Me); 1.44 – 1.57 (m, Me2CH); 2.81 (d, J ¼ 5.0,
HꢀC(3)); 3.26 (sept., J ¼ 6.4, Me2CH); 4.16 (d, J ¼ 5.0, HꢀC(4)); 4.34, 4.78 (2d, 1:1, J ¼ 14.7, CH2); 5.09,
5.16 (2d, 1:1, J ¼ 12.0, CH2); 5.16 (br. s, NH); 7.27 – 7.40 (m, 10 arom. H). 13C-NMR ((D6)DMSO): 16.5;
18.1; 18.3; 20.3; 32.8; 48.0; 52.0; 55.7; 65.1; 67.4; 128.0; 128.5; 128.5; 128.5; 128.7; 129.2; 136.2; 136.2;
156.0; 168.4. ESI-MS: 410 ([M þ H]þ). HR-ESI-MS: 410.2438 ([M þ H]þ, C24H32N3Oþ3 ; calc. 410.2438).
Anal. calc. for C24H31N3O3 (409.52): C 70.39, H 7.63, N 10.26; found: C 70.39, H 7.85, N 10.25.
9.3. Ethyl [(3RS,4RS)-4-{[(Benzyloxy)carbonyl]amino}-5-oxo-2,3-di(propan-2-yl)pyrazolidin-1-
yl]acetate (12c). Prepared from 10d (319 mg, 1 mmol) and 11c (118 ml, 1.3 mmol); 48 h; CC (AcOEt/
hexanes 1:2). Yield: 307 mg (76%). Colorless semisolid. M.p. 81 – 838. IR (KBr): 3302, 3053, 3032, 2970,
2906, 2863, 1745, 1720, 1677, 1535, 1474, 1455, 1435, 1417, 1383, 1372, 1328, 1291, 1233, 1196, 1179, 1149,
1
1120, 1107, 1072, 1051, 1027, 989, 965, 949, 933, 909, 874, 856, 842, 801, 777, 757, 734, 705, 654. H-NMR
((D6)DMSO): 0.95 (d, J ¼ 5.4, Me); 0.98 – 1.04 (m, 2 Me); 1.08 (d, J ¼ 6.8, Me); 1.27 (t, J ¼ 7.2, MeCH2);
1.80 – 1.90 (m, Me2CH); 2.87 (d, J ¼ 3.2, HꢀC(3)); 3.16 (sept., J ¼ 6.5, Me2CH); 4.05, 4.23 (2d, 1:1, J ¼
17.0, CH2); 4.13 – 4.26 (m, MeCH2, HꢀC(4)); 5.10, 5.16 (2d, 1:1, J ¼ 12.1, CH2); 5.22 (br. s, NH);
7.30 – 7.44 (m, 5 arom. H). 13C-NMR ((D6)DMSO): 14.3; 17.3; 18.6; 18.7; 20.2; 32.6; 47.1; 53.6; 55.4; 61.8;
66.6; 67.5; 128.4; 128.5; 128.8; 136.1; 155.9; 167.7; 169.5. ESI-MS: 406 ([M þ H]þ). HR-ESI-MS: 406.2336

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([M þ H]þ, C21H32N3Oþ5 ; calc. 406.2336). Anal. calc. for C21H31N3O5 (405.49): C 62.20, H 7.71, N 10.36);
found: C 62.36, H 7.76, N 10.46.
9.4. tert-Butyl [(3RS,4RS)-4-{[(Benzyloxy)carbonyl]amino}-5-oxo-2,3-di(propan-2-yl)pyrazolidin-
1-yl]acetate (12d). Prepared from 10d (319 mg, 1 mmol) and 11d (192 ml, 1.3 mmol); 48 h; CC (AcOEt/
hexanes 1:2). Yield: 228 mg (53%). Colorless oil. IR (NaCl): 3282, 3034, 2971, 2936, 2875, 1720, 1678,
1530, 1455, 1390, 1368, 1334, 1298, 1249, 1222, 1152, 1046, 1027, 982, 941, 920, 846, 803, 774, 752, 735, 697.
1H-NMR ((D6)DMSO): 0.94 (d, J ¼ 5.3, Me); 1.01 (d, J ¼ 6.4, 2 Me); 1.08 (d, J ¼ 6.8, Me); 1.46 (s, t-Bu);
1.81 – 1.90 (m, Me2CH); 2.85 (d, J ¼ 4.9, HꢀC(3)); 3.15 (sept., J ¼ 6.7, Me2CH); 3.95, 4.12 (2d, 1:1, J ¼
16.8, CH2); 4.21 (d, J ¼ 4.9, HꢀC(4)); 5.09, 5.15 (2d, 1 :1, J ¼ 12.2, CH2); 5.28 (d, J ¼ 6.6, NH); 7.30 –
7.38 (m, 5 arom. H). 13C-NMR ((D6)DMSO): 17.5; 18.6; 18.7; 20.1; 28.2; 32.5; 48.0; 53.6; 55.5; 66.6;
67.4; 82.5; 128.4; 128.4; 128.7; 136.2; 155.9; 166.7; 169.3. ESI-MS: 434 ([M þ H]þ). HR-ESI-MS: 434.2647
([M þ H]þ, C23H36N3Oþ5 ; calc. 434.2649).
9.5. Benzyl [(4RS,5RS)-1-Benzyl-2-methyl-3-oxo-5-(propan-2-yl)pyrazolidin-4-yl]carbamate (12e).
Prepared from 10e (928 mg, 2.5 mmol) and 11a (568 ml, 8.25 mmol); 72 h; CC (AcOEt/hexanes 1:1).
Yield: 661 mg (70%). White solid. M.p. 113 – 1158. IR (KBr): 3230, 3052, 3031, 3009, 2964, 2950, 2931,
2894, 2872, 1707, 1660, 1586, 1544, 1496, 1458, 1389, 1365, 1351, 1324, 1305, 1271, 1245, 1217, 1177, 1159,
1136, 1111, 1095, 1083, 1043, 1026, 1002, 991, 979, 919, 863, 820, 808, 767, 751, 719, 700, 646, 620. 1H-NMR
((D6)DMSO): 0.80 – 0.94 (m, 2 Me); 1.65 – 1.82 (m, Me2CH); 2.95 (dd, J ¼ 2.5, 5.2, HꢀC(5)); 3.07 (s,
MeꢀC(2)); 3.89, 4.05 (2d, 1:1, CH2),3.99 (dd, J ¼ 2.5, 7.5, HꢀC(4)); 4.12 (d, J ¼ 7.2, NH); 5.08 (s, CH2);
7.18 – 7.24, 7.30 – 7.43 (2m, 1:4, 10 arom. H). 13C-NMR ((D6)DMSO): 17.4; 18.7; 30.6; 32.1; 55.6; 60.2;
67.1; 69.9; 128.1; 128.3; 128.6; 128.7; 128.9; 130.4; 135.2; 136.4; 155.8; 168.4. ESI-MS: 382 ([M þ H]þ).
HR-ESI-MS: 382.2123 ([M þ H]þ, C22H28N3O3þ ; calc. 382.2125). Anal. calc. for C22H27N3O3 (381.47):
C 69.27, H 7.13, N 11.02; found: C 69.40, H 7.35, N 11.25.
9.6. Benzyl [(4RS,5RS)-1,2-Dibenzyl-3-oxo-5-(propan-2-yl)pyrazolidin-4-yl]carbamate (12f). Pre-
pared from 10e (367 mg, 1 mmol) and 11b (119 ml, 1 mmol); 72 h; CC (AcOEt/hexanes 1:3). Yield:
334 mg (73%). White solid. M.p. 150 – 1538. IR (KBr): 3249, 3083, 3061, 3029, 3010, 2974, 2947, 2923,
2891, 2868, 1956, 1725, 1657, 1542, 1495, 1454, 1422, 1384, 1367, 1344, 1319, 1238, 1176, 1157, 1137, 1120,
1085, 1049, 1028, 1008, 989, 970, 958, 938, 913, 868, 846, 812, 766, 751, 730, 700, 666, 617. 1H-NMR
((D6)DMSO): 0.50 (d, J ¼ 4.8, Me); 0.72 (br. s, Me); 1.29 – 1.40 (m, Me2CH); 2.79 (d, J ¼ 7.2, HꢀC(5));
3.91, 3.97 (2d, 1:1, J ¼ 13.2, CH2); 3.99 (d, J ¼ 7.2, HꢀC(4)); 4.28, 4.97 (2d, 1:1, CH2); 4.29 (s, HNꢀC(4));
5.07 (s, CH2); 7.12 – 7.15, 7.29 – 7.44 (2m, 1:14, 15 arom. H). 13C-NMR ((D6)DMSO): 18.3; 18.5; 31.3; 47.3;
55.9; 60.8; 67.1; 70.5; 128.1; 128.2; 28.3; 128.4; 128.6; 128.7; 128.8; 129.3; 130.4; 135.4; 136.1; 136.4; 155.8;
168.8. ESI-MS: 458 ([M þ H]þ). HR-ESI-MS: 458.2435 ([M þ H]þ, C28H32N3Oþ3 ; 458.2438). Anal. calc.
for C28H31N3O3 (457.24): C 73.50, H 6.83, N 9.18; found: C 73.32, H 7.02, N 9.20.
9.7. Ethyl [(3RS,4RS)-2-Benzyl-4-{[(benzyloxy)carbonyl]amino}-5-oxo-3-(propan-2-yl)pyrazoli-
din-1-yl]acetate (12g). Prepared from 10e (367 mg, 1 mmol) and 11c (118 ml, 1.3 mmol); 24 h; CC
(AcOEt/hexanes 1:3). Yield: 437 mg (97%). Colorless semisolid. IR (KBr): 3216, 3049, 3025, 2995, 2975,
2958, 2940, 2873, 1756, 1728, 1665, 1604, 1549, 1496, 1480, 1455, 1430, 1392, 1371, 1347, 1248 1201, 1159,
1134, 1119, 1069, 1045, 1026, 989, 970, 954, 939, 926, 903, 863, 847, 816, 769, 732, 697, 679. 1H-NMR
((D6)DMSO): 0.89 (d, J ¼ 5.8, Me); 0.94 (br. s, Me); 1.25 (t, J ¼ 7.1, MeCH2); 1.76 – 1.87 (m, Me2CH);
2.88 (br. s, HꢀC(3)); 3.87, 4.30 (2d, 1:1, J ¼ 17.0, CH2); 3.95, 4.01 (2d, 1:1, J ¼ 13.4, CH2); 4.10 – 4.20 (m,
MeCH2, HꢀC(4)); 4.53 (br. s, NH); 5.09 (s, CH2); 7.23 – 7.28, 7.30 – 7.40 (2m, 1:4, 10 arom. H). 13C-NMR
((D6)DMSO): 14.3; 18.6; 19.1; 31.1; 46.3; 55.3; 61.6; 61.8; 67.2; 71.9; 128.2; 128.4; 128.5; 128.7; 128.9;
130.1; 135.7; 136.3; 155.8; 167.6; 170.0. ESI-MS: 454 ([M þ H]þ). HR-ESI-MS: 454.2337 ([M þ H]þ,
C25H32N3Oþ5 ; calc. 454.2336). Anal. calc. for C25H31N3O5 (453.53): C 66.21, H 6.89, N 9.27; found: C 66.23,
H 7.13, N 9.18.
9.8. Benzyl [(4RS,5RS)-1-Benzyl-2-methyl-3-oxo-5-phenylpyrazolidin-4-yl]carbamate (12h). Pre-
pared from 10j (402 mg, 1 mmol) and 11a (227 ml, 3.3 mmol), 48 h, CC: AcOEt/hexanes 1:3. Yield:
210 mg (50%). Colorless oil. IR (NaCl): 3291, 3060, 3030, 2923, 2853, 2154, 1682, 1605, 1538, 1496, 1481,
1454, 1425, 1397, 1369, 1344, 1293, 1253, 1210, 1189, 1106, 1056, 1029, 993, 916, 872, 780, 752, 730, 713, 696,
659. 1H-NMR ((D6)DMSO): 3.05 (s, Me); 3.98, 4.09 (2d, 1:1, J ¼ 14.4, CH2); 4.20 (br. s, HꢀC(5)); 4.26
(br. t, J ¼ 7.3, HꢀC(4)); 4.98 (br. s, NH); 5.08 (s, CH2); 7.22 – 7.38, 7.44 – 7.48 (2m, 13 :2, 15 H, Ph).
13C-NMR ((D6)DMSO): 31.9; 59.5; 60.6; 67.4; 69.5; 127.4; 128.2; 128.3; 128.3; 128.4; 128.7; 128.8; 128.9;

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129.3; 136.1; 136.2; 138.4; 156.1; 167.5. ESI-MS: 416 ([M þ H]þ). HR-ESI-MS: 416.1966 ([M þ H]þ,
C25H26N3Oþ3 ; calc. 416.1969).
10. General Procedure for Preparation of Amines 13 – 15 (GP 6). A mixture of 5, 10, or 12 (1 mmol),
EtOH (20 ml), and 10% Pd/C (50 – 100 mg) was hydrogenated (3.5 bar of H2) at r.t. for 1 – 17 h. The
catalyst was removed by filtration, washed with EtOH (2 ꢂ 5 ml), and the combined filtrate was
evaporated in vacuo to give 13, 14, or 15, resp.
10.1. (4RS,5RS)-4-Amino-5-(propan-2-yl)pyrazolidin-3-one (13). Prepared from 5c (1.37 g,
4.95 mmol), EtOH (50 ml), and 10% Pd/C (200 mg); 2.5 h. Yield: 707 mg (100%). White solid. M.p.
118 – 1228. IR (KBr): 3355, 3283, 2966, 2872, 2858, 1726, 1684, 1601, 1507, 1471, 1385, 1334, 1311, 1213,
1174, 1112, 1042, 983, 962, 947, 910, 869, 846, 712, 668. 1H-NMR ((D6)DMSO): 0.90, 0.97 (2d, 1:1, J ¼ 6.8,
2 Me); 1.75 (sept., J ¼ 6.8, Me2CH); 2.64 (t, J ¼ 8.7, HꢀC(5)); 3.10 (d, J ¼ 9.7, HꢀC(4)); 3.34 (br. s, NH2);
4.84 (br. s, HꢀN(1)); 9.12 (s, HꢀN(2)).13C-NMR ((D6)DMSO): 19.5; 19.5; 30.3; 56.5; 71.9; 177.2. ESI-
MS: 144 ([M þ H]þ). HR-ESI-MS: 144.1133 ([M þ H]þ, C6H14N3Oþ; calc. 144.1059). Anal. calc. for
C6H13N3O (143.19): C 50.33, H 9.15, N 29.35; found: C 50.37, H 8.94, N 25.52.
10.2. (4RS,5RS)-4-Amino-1,5-di(propan-2-yl)pyrazolidin-3-one (14a). Prepared from 10d (500 mg,
1.57 mmol), EtOH (40 ml), 10% Pd/C (90 mg), 3.5 h. Yield: 289 mg (100%). Brown semisolid.
IR(NaCl): 3367, 3348, 3286, 3140, 2966, 2934, 2871, 1669, 1461, 1387, 1368, 1343, 1329, 1180, 1154, 1126,
1086, 1062, 1026, 956, 938, 922, 891, 865, 846, 826, 793, 713, 656. 1H-NMR (CDCl3): 0.95, 0.97 (2d, 1:1, J ¼
7.0, 2 Me); 1.08, 1.12 (2d, 1:1, J ¼ 6.4, 2 Me); 1.67 (br. s, NH2); 1.78 (sept., J ¼ 6.9, Me2CH); 2.78 (dd, J ¼
4.3, 5.8, HꢀC(5)); 2.94 (sept., J ¼ 6.3, Me2CH); 3.27 (d, J ¼ 4.2, HꢀC(4)); 8.18 (br. s, HꢀN(2)). 13C-NMR
(CDCl3): 17.7; 18.0; 18.6; 20.9; 32.2; 55.8; 57.3; 72.5; 174.4. ESI-MS: 186 ([M þ H]þ). HR-ESI-MS:
186.1601 ([M þ H]þ, C9H20N3Oþ; calc. 186.1601).
10.3. (4RS,5RS)-4-Amino-1-benzyl-5-(propan-2-yl)pyrazolidin-3-one (14b). Prepared from 10e
(205 mg, 0.56 mmol), EtOH (20 ml), 10% Pd/C (10 mg); 17 h. Yield: 105 mg (90%). Brown oil. IR
(NaCl): 3025, 2960, 2931, 2895, 2868, 1681, 1602, 1588, 1575, 1494, 1467, 1455, 1434, 1393, 1382, 1366, 1349,
1317, 1303, 1262, 1179, 1134, 1082, 1066, 1029, 975, 899, 854, 833, 740, 698, 643. 1H-NMR ((D6)DMSO):
0.79, 0.81 (2d, 1:1, J ¼ 6.9, 2 Me); 1.62 (sept., J ¼ 6.6, Me2CH); 2.62 (t, J ¼ 5.3, HꢀC(5)); 3.04 (d, J ¼ 5.0,
HꢀC(4)); 3.83, 3.96 (2d, J ¼ 13.0, CH2); 7.22 – 7.40 (m, 5 arom. H); 9.40 (s, HꢀN(2)); NH2 exchanged.
13C-NMR (CDCl3): 18.4; 18.8; 30.6; 55.4; 64.7; 75.7; 128.2; 128.8; 129.6; 136.2; 173.6. ESI-MS: 234 ([M þ
H]þ). HR-ESI-MS: 234.16 ([M þ H]þ, C13H20N3Oþ; calc. 234.1601).
10.4. (4RS,5RS)-4-Amino-1-benzyl-2-methyl-5-(propan-2-yl)pyrazolidin-3-one (15a). Prepared
from 12e (551 mg, 1.44 mmol), EtOH (20 ml), 10% Pd/C (100 mg), 1 h. Yield: 345 mg (97%). Brown
oil. IR (NaCl): 3360, 3293, 3087, 3062, 3031, 2985, 2931, 2872, 1667, 1603, 1495, 1466, 1454, 1427, 1394,
1365, 1297, 1261, 1205, 1066, 1028, 1005, 971, 916, 880, 842, 795, 754, 726, 699, 636. 1H-NMR
((D6)DMSO): 0.83, 0.84 (2d, 1:1, J ¼ 6.7, 2 Me); 1.45 (br. s, NH2); 1.60 – 1.69 (dsept., J ¼ 1.3, 6.6, Me2CH);
2.77 (dd, J ¼ 2.8, 5.5, HꢀC(5)); 3.03 (s, Me); 3.16 (d, J ¼ 2.8, HꢀC(4)); 3.98, 4.09 (2d, 1:1, J ¼ 13.4, CH2);
7.28 – 7.43 (m, 5 arom. H).13C-NMR ((D6)DMSO): 17.7; 18.4; 30.5; 32.2; 56.4; 60.6; 71.3; 128.3; 128.8;
130.3; 135.7; 172.4. ESI-MS: 248 ([M þ H]þ). HR-ESI-MS: 248.1769 ([M þ H]þ, C14H22N3Oþ; calc.
248.1685).
10.5. (4RS,5RS)-4-Amino-1-benzyl-2-methyl-5-phenylpyrazolidin-3-one (15b). Prepared from 12h
(100 mg, 0.24 mmol), EtOH (20 ml), 10% Pd/C (10 mg); 1 h. Yield: 63 mg (94%). Purple oil. IR (NaCl):
3369, 3304, 3086, 3062, 3030, 3006, 2922, 2860, 1685, 1602, 1495, 1475, 1454, 1423, 1394, 1365, 1305, 1285,
1250, 1199, 1157, 1096, 1070, 1028, 1002, 967, 909, 851, 790, 729, 698, 643. 1H-NMR ((D6)DMSO): 1.87 (br.
s, NH2); 2.98 (s, J ¼ 6.8, Me); 3.54 (d, J ¼ 9.7, HꢀC(4)); 3.71 (d, J ¼ 9.7, HꢀC(5)); 3.83, 4.10 (2d, 1:1, J ¼
14.6, CH2); 7.23 – 7.45 (m, 10 arom. H).13C-NMR ((D6)DMSO): 32.0; 59.1; 60.7; 73.4; 127.8; 127.8; 128.4;
128.6; 129.0; 129.0; 136.5; 138.4; 170.9. ESI-MS: 282 ([M þ H]þ). HR-ESI-MS: 282.16 ([M þ H]þ,
C17H20N3Oþ; calc. 282.1601).
11. General Procedure for the Preparation of 1,5-Disubstituted (4RS,5RS)-4-Alkylaminopyrazolidin-
3-ones 16 (GP 7). A mixture of 10 (1 mmol), MeOH (10 ml), carbonyl compound 6 (1 mmol), 1m aq.
HCl (2 drops), and 10% Pd/C (30 mg) was hydrogenated (3.5 bar of H2) at r.t. 4 – 13 h. The catalyst was
removed by filtration, washed with MeOH (2 ꢂ 5 ml), and the combined filtrate was evaporated in vacuo
to give 16.

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11.1. (4RS)-1-(Propan-2-yl)-4-(propan-2-ylamino)pyrazolidin-3-one (16a). Prepared from 10a
(277mg, 1 mmol) and 6 [4] (10 ml, excess), 5 h. Yield: 185 mg (100%). Reddish solid. M.p. 60 – 648. IR
1
(KBr): 3418, 2973, 2834, 1694, 1470, 1387, 1338, 1179, 1065, 1014, 901, 838, 771, 657. H-NMR (CDCl3):
0.97, 0.99, 1.00, 1.02 (4d, 1:1:1:1, J ¼ 6.4, 4 Me); 1.91 (s, NH); 2.73 (br. s, HaꢀC(5)); 2.89 – 2.98 (sept., J ¼
6.4, Me2CH); 3.16 (s, HbꢀC(5)); 3.52 (dd, J ¼ 10.5, 7.9, HꢀC(4)); 3.60 (br. s, Me2CH); 9.59 (s, HꢀN(2)).
13C-NMR (CDCl3): 19.3; 20.0; 22.7; 22.9; 48.5; 56.1; 57.5; 57.9; 173.8. ESI-MS: 186 ([M þ H]þ). HR-ESI-
MS: 186.1592 ([M þ H]þ, C9H20N3Oþ; calc. 186.1601).
11.2. (4RS,5RS)-4-(Butylamino)-1,5-di(propan-2-yl)pyrazolidin-3-one (16b). Prepared from 10d
(250 mg, 0.78 mmol) and 6b (98 ml, 1 mmol), 9 h. Yield: 227 mg (100%). Yellow oil. IR (NaCl): 3176,
2932, 2959, 2873, 1689, 1467, 1385, 1368, 1203, 1166, 1104, 1006, 838, 798, 768, 665. 1H-NMR
((D6)DMSO): 0.83 – 0.90 (m, Me2CH, MeCH2); 0.96, 0.98 (2d, 1:1, J ¼ 6.4, Me2CH); 1.25 – 1.42 (m,
2 CH2); 1.56 (sept., Me2CH); 1.76 (br. s, NH); 2.51 – 2.59, 2.60 – 2.68 (2m, 1:1, CH2); 2.79 (dd, J ¼ 2.4, 5.9,
HꢀC(5)); 2.81 (br. d, J ¼ 2.4, HꢀC(4)); 2.95 (sept., J ¼ 6.3, Me2CH); 9.41 (s, HꢀN(2)). 13C-NMR
((D6)DMSO): 13.7; 16.4; 18.2; 19.4; 19.9; 20.8; 31.7; 35.9; 47.5, 56.9, 61.6, 69.6, 172.7. ESI-MS: 252 ([M þ
H]þ). HR-ESI-MS: 242.2227 ([M þ H]þ, C13H28N3Oþ; calc. 242.2227).
11.3. (4RS,5RS)-1,5-Di(propan-2-yl)-4-(propan-2-ylamino)pyrazolidin-3-one (16c). Prepared from
10d (319 mg, 1 mmol) and 6d (10 ml); 5 h. Yield: 227 mg (100%). Yellow oil. IR (NaCl): 3174, 3062,
1
2965, 2873, 1689, 1469, 1384, 1366, 1321, 1167, 1022, 944, 856. H-NMR ((D6)DMSO): 0.87 (d, J ¼ 6.7,
Me2CH); 0.96, 0.98, 0.99, 1.00 (4d, 1:1:1:1, J ¼ 6.4, 2 Me2CH); 1.55 (br. s, NH); 1.58 (sept., J ¼ 6.4,
Me2CH); 2.78 (dd, J ¼ 2.1, 5.8, HꢀC(5)); 2.92 (d, J ¼ 2.1, HꢀC(4)); 2.93 – 3.00 (m, 2 Me2CH); 9.40 (s,
HNꢀC(4)). 13C-NMR ((D6)DMSO): 18.1; 18.4; 19.4; 20.8; 22.9; 22.9; 31.8; 46.3; 56.8; 58.8; 70.3; 137.2.
ESI-MS: 228 ([M þ H]þ). HR-ESI-MS: 228.2069 ([M þ H]þ, C12H26N3Oþ; calc. 228.207).
11.4. (4RS,5RS)-4-(Cyclohexylamino)-1,5-di(propan-2-yl)pyrazolidin-3-one (16d). Prepared from
10d (319 mg, 1 mmol) and 6e (0.1036 ml, 1 mmol); 6 h. Yield: 286 mg (100%). Yellow oil. IR (NaCl):
3168, 3066, 2928, 2688, 1450, 1385, 1369, 1324, 1126, 1016, 948, 890, 846, 802. 1H-NMR ((D6)DMSO): 0.87,
0.96, 0.98 (3d, 2 :1:1, J ¼ 6.6, 2 Me2CH); 0.94 – 1.00 (m, 1 H, C6H11); 1.08 – 1.25 (m, 3 H, C6H11); 1.51 – 1.61
(m, 3 H, C6H11, Me2CH); 1.62 – 1.69 (m, 2 H, C6H11); 1.82 – 1.90 (m, 2 H, C6H11); 2.56 – 2.65 (m, 1 H,
C6H11); 2.78 (dd, J ¼ 2.3, 5.9, HꢀC(5)); 2.96 (sept., J ¼ 6.3, Me2CH); 2.98 – 3.01 (m, HꢀC(4)); 3.34 (s,
NH); 9.39 (s, HꢀN(2)). 13C-NMR ((D6)DMSO): 18.2; 18.4; 19.3; 20.8; 24.6; 24.7; 25.8; 31.8; 33.2; 33.3;
54.1; 56.9; 58.3; 70.4; 173.2. ESI-MS: 287 ([M þ H]þ). HR-ESI-MS: 267.2311 ([M þ H]þ, C15H30N3Oþ;
calc. 268.2383).
11.5. (4RS,5RS)-1,5-Di(propan-2-yl)-4-(propylamino)pyrazolidin-3-one (16e). Prepared from 10d
(319 mg, 1 mmol) and 6n (89 ml, 1.2 mmol); 5 h. Yield: 218 mg (96%). Dark-red oil. IR (NaCl): 3186,
1
2961, 2873, 1688, 1464, 1385, 1325, 1129, 948, 880, 794. H-NMR ((D6)DMSO): 0.82 – 0.89 (m, MeCH2,
Me2CH); 0.96, 0.98 (2d, 1:1, J ¼ 6.4, Me2CH); 1.36 – 1.46 (m, CH2); 1.56 (sept., Me2CH); 1.78 (br. s,
HNꢀC(4)); 2.47 – 2.56, 2.57 – 2.66 (2m, 1:1, CH2); 2.79 (dd, J ¼ 2.2, 5.9, HꢀC(5)); 2.82 (br. s, HꢀC(4));
2.96 (sept., J ¼ 6.4, Me2CH); 9.41 (s, HꢀN(2)). 13C-NMR ((D6)DMSO): 18.1; 18.2; 19.3; 20.8; 31.6; 31.8;
35.9; 47.4; 56.8; 61.6; 69.6; 172.7. ESI-MS: 228 ([M þ H]þ). HR-ESI-MS: 228.207 ([M þ H]þ,
C12H26N3Oþ; calc. 228.207).
11.6. (4RS,5RS)-4-(Pentan-2-ylamino)-1,5-di(propan-2-yl)pyrazolidin-3-one (16f). Prepared from
10d (319 mg, 1 mmol) and 6o (5 ml, excess); 13 h. Yield: 192 mg (75%), 2 :1 mixture of diastereoisomers.
Red oil. IR (NaCl): 3177, 3066, 2960, 2931, 2872, 1690, 1467, 1384, 1370, 1326, 1155, 1069, 1006, 946, 767,
1
692. H-NMR (CDCl3): major isomer: 0.84 – 0.92 (m, Me2CH, MeCH2); 1.01 – 1.06 (m, Me2CH, 3 H of
pentyl); 1.20 – 1.43 (m, 2 CH2); 1.59 – 1.71 (m, Me2CH); 2.70 (sext., J ¼ 6.2, 1 H, CH2); 2.80 (dd, J ¼ 2.0,
6.0, HꢀC(5)); 2.97 (br. tq, J ¼ 3.4, 6.3, 1 H, CH2); 3.05 (sept., J ¼ 6.4, Me2CH); 3.17 (br. d, J ¼ 1.8,
HꢀC(4)); 9.09 (br. s, HꢀN(2)); minor isomer: 0.84 – 0.92 (m, Me2CH, MeCH2); 1.01 – 1.06 (m, Me2CH,
3 H of pentyl); 1.20 – 1.43 (m, 2 CH2); 1.59 – 1.71 (m, Me2CH); 2.70 (sext., J ¼ 6.2, Me2CH); 2.80 (dd, J ¼
2.0, 6.0, HꢀC(5)); 2.97 (br. tq, J ¼ 3.4, 6.3, 1 H, CH2); 3.05 (sept., J ¼ 6.4, Me2CH); 3.13 (br. d, J ¼ 2.2,
HꢀC(4)); 9.09 (br. s, HꢀN(2)). 13C-NMR (CDCl3): major isomer: 14.3; 18.4; 18.8; 19.3; 19.4; 20.4; 20.9;
32.2; 40.0; 50.8; 57.9; 59.6; 71.1; 174.7; minor isomer: 14.3; 18.2; 18.7; 19.2; 19.2; 20.7; 20.9; 32.4; 39.5;
50.3; 57.8; 59.3; 71.6; 174.6. ESI-MS: 256 ([M þ H]þ). HR-ESI-MS: 256.238 ([M þ H]þ, C14H30N3Oþ;
calc. 256.2383).

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Helvetica Chimica Acta – Vol. 97 (2014)
11.7. (4RS,5RS)-4-(Cyclopentylamino)-1,5-di(propan-2-yl)pyrazolidin-3-one (16g). Prepared from
10d (319 mg, 1 mmol) and 6p (89 ml, 1 mmol); 12 h. Yield: 234 mg (99%). Dark oil. IR (NaCl): 3180,
3066, 2958, 2871, 1689, 1571, 1466, 1385, 1368, 1324, 1203, 1169, 1012, 958, 888, 830, 799. 1H-NMR
((D6)DMSO): 0.86, 0.87 (2d, 1:1, J ¼ 6.7, Me2CH); 0.96, 0.98 (2d, 1:1, J ¼ 6.3, Me2CH); 1.24 – 1.33, 1.40 –
1.50 (2m, 1:1, CH2); 1.53 – 1.63 (m, CH2, Me2CH); 1.69 – 1.81 (m, CH2, C5H9); 2.04 – 2.10 (m, NH); 2.81
(dd, J ¼ 5.9, 2.2, HꢀC(5)); 2.86 (d, J ¼ 2.2, HꢀC(4)); 2.95 (sept., J ¼ 6.3, Me2CH); 3.27 (quint., J ¼ 6.5,
1 H, C5H9); 9.40 (s, HꢀN(2)). 13C-NMR ((D6)DMSO): 18.2; 18.4; 19.8; 20.8; 22.7; 31.8; 32.6; 32.7; 37.8;
56.8; 57.7; 60.1; 70.0; 173.0. ESI-MS: 254 ([M þ H]þ). HR-ESI-MS: 254.223 ([M þ H]þ, C14H28N3Oþ;
calc. 254.2227).
11.8. (4RS,5RS)-4-(Cycloheptylamino)-1,5-di(propan-2-yl)pyrazolidin-3-one (16h). Prepared from
10d (319 mg, 1 mmol) and 6q (0.168 ml, 1.4 mmol); 13 h. Yield: 281 mg (100%). Yellow oil. IR (NaCl):
3171, 3062, 2965, 2926, 2855, 1688, 1463, 1385, 1368, 1324, 1125, 1016, 950, 825, 772, 688. 1H-NMR
((D6)DMSO): 0.86, 0.87 (2d, 1:1, J ¼ 6.7, Me2CH); 0.96, 0.98 (2d, 1:1, J ¼ 6.3, Me2CH); 1.26 – 1.39 (m,
4 H, C7H14); 1.42 – 1.65 (m, 4 CH2, C7H14, Me2CH); 1.75 – 1.85 (m, NH); 2.77 (dd, J ¼ 2.3, 6.0, HꢀC(5));
2.80 – 2.86 (m, 1 H, C7H14); 2.92 (d, J ¼ 2.3, HꢀC(4)); 2.96 (sept., J ¼ 6.3, Me2CH); 9.39 (s, HꢀN(2)).
13C-NMR (CDCl3): 18.3; 18.6; 19.2; 20.9; 24.1; 24.2; 28.2; 28.4; 32.3; 34.7; 35.3; 56.9; 57.8; 59.2; 71.5;
174.5. ESI-MS: 282 ([M þ H]þ). HR-ESI-MS: 282.2541 ([M þ H]þ, C16H32N3Oþ; calc. 282.254).
11.9. (4RS,5RS)-1,5-Di(propan-2-yl)-4-[(tetrahydrofuran-3-ylmethyl)amino]pyrazolidin-3-one
(16i). Prepared from 10d (319 mg, 1 mmol) and 6r (50% aq. soln., 0.227 ml, 1.3 mmol); 4 h. Yield:
269 mg (100%); 1:1 mixture of diastereoisomers. Yellow oil. IR (NaCl): 3232, 2966, 2872, 1686, 1468,
1
1386, 1369, 1325, 1204, 1156, 1130, 1076, 912, 801, 762. H-NMR (CDCl3): diastereoisomer 1: 0.93, 0.95
(2d, 1:1, J ¼ 6.8, Me2CH); 1.06 – 1.10 (m, Me2CH); 1.53 – 1.66 (m, 1 H, CH2); 1.70 (sept., J ¼ 6.7, Me2CH);
2.00 – 2.08 (m, 1 H, CH2); 2.29 – 2.45 (m, 2 H, NH, CH2); 2.58 (dd, J ¼ 8.6, 11.0, 1 H, CH2); 2.77 – 2.85 (m,
1 H, CH2); 2.83 (dd, J ¼ 2.6, 6.1, HꢀC(5)); 3.02 (sept., J ¼ 6.4, Me2CH); 3.09 (br. d, J ¼ 2.6, HꢀC(4)); 3.50
(dd, J ¼ 5.9, 8.7, 1 H, CH2); 3.70 – 3.90 (m, 3 H, CH2); HꢀN(2) exchanged; diastereoisomer 2: 0.93, 0.95
(2d, 1:1, J ¼ 6.8, Me2CH); 1.06 – 1.10 (m, Me2CH); 1.53 – 1.66 (m, 1 H, CH2); 1.70 (sept., J ¼ 6.7, Me2CH);
2.00 – 2.08 (m, 1 H, CH2); 2.29 – 2.45 (m, 2 H, NH, CH2); 2.65 (dd, J ¼ 7.6, 11.2, 1 H, CH2); 2.77 – 2.85 (m,
1 H, CH2); 2.83 (dd, J ¼ 2.6, 6.1, HꢀC(5)); 3.02 (sept., J ¼ 6.4, Me2CH); 3.12 (br. d, J ¼ 2.6, HꢀC(4)); 3.54
(dd, J ¼ 5.9, 8.7, 1 H, CH2); 3.70 – 3.90 (m, 3 H, CH2); HꢀN(2) exchanged. 13C-NMR (CDCl3):
diastereoisomer 1: 18.3; 18.5; 18.9; 21.0; 30.5; 32.3; 39.8; 51.3; 57.7; 62.1; 67.8; 70.6; 71.8; 173.6;
diastereoisomer 2: 18.4; 18.5; 18.9; 21.0; 30.6; 32.3; 39.8; 52.0; 57.8; 62.4; 67.9; 70.7; 72.2; 173.7. ESI-MS:
270 ([M þ H]þ). HR-ESI-MS: 270.2176 ([M þ H]þ, C14H28N3Oþ2 ; calc. 270.2176).
12. Synthesis of N-[(4RS,5RS)-3-Oxo-5-(propan-2-yl)pyrazolidin-4-yl]-1,1’-biphenyl-4-carboxamide
(17). A mixture of 20a (153 mg, 0.77 mmol), DMF (5 ml), Et3N (0.107 ml, 0.77 ml), and BPC (303 mg,
0.77 mmol) was stirred under Ar at r.t. for 2 h. Then, Et3N (0.107 ml, 0.77 ml) and amine 13 (110 mg,
0.77 mmol) were added, and the mixture was stirred at r.t. for 12 h. Volatile components were evaporated
in vacuo, and the residue was purified by FC (first AcOEt to elute the less-polar impurities, then AcOEt/
MeOH 20 :1, to elute the product). Fractions containing the product were combined and evaporated in
vacuo. The residue was triturated with CH2Cl2 (5 ml), and the precipitate was collected by filtration to
give 17. Yield: 26 mg (10%). White solid. M.p. 221 – 2238. IR (KBr): 3266, 3067, 2955, 2922, 2867, 1724,
1640, 1607, 1561, 1536, 1499, 1482, 1448, 1426, 1403, 1388, 1364, 1313, 1294, 1277, 1258, 1194, 1179, 1108,
1077, 1006, 977, 912, 852, 819, 808, 767, 744, 728, 693. 1H-NMR ((D6)DMSO): 0.89, 0.92 (2d, 1:1, J ¼ 6.6,
Me2CH); 1.78 – 1.90 (m, Me2CH); 3.16 (dd, J ¼ 8.8, 10.4, HꢀC(5)); 4.62 (dd, J ¼ 9.2, 10.7, HꢀC(4)); 5.05
(br. s, HꢀN(1)); 7.40 – 8.06 (m, 9 arom. H); 8.76 (d, J ¼ 9.0, NH); 9.34 (s, HꢀN(2)). 13C-NMR
((D6)DMSO): 18.7; 19.8; 21.2; 24.7; 30.3; 126.6; 126.9; 127.9; 128.3; 129.0; 130.0; 132.9; 139.1; 165.7; 167.2.
ESI-MS: 324 ([M þ H]þ). HR-ESI-MS: 324.1706 ([M þ H]þ, C19H22N3Oþ2 ; calc. 324.1707).
13. General Procedure for the Synthesis of 4-[(Phenylacetyl)amino]pyrazolidin-3-ones 18 and 19
(GP 8). A mixture 14a or 15a (1 mmol), anh. CH2Cl2 (5 ml), 20b (141 mg, 1.04 mmol), and EEDQ
(270 mg, 1.09 mmol) was stirred under Ar for 24 h. Volatile components were evaporated in vacuo, and
the residue was purified by CC (AcOEt/hexanes 1:1). Fractions containing the product were combined
and evaporated in vacuo to give 18 or 19.
13.1. N-[(4RS,5RS)-3-Oxo-1,5-di(propan-2-yl)pyrazolidin-4-yl]-2-phenylacetamide (18). Prepared
from 14a (168 mg, 0.91 mmol). Yield: 229 mg (83%). White solid. M.p. 155 – 1608. IR (KBr): 3374, 3239,

Helvetica Chimica Acta – Vol. 97 (2014)
265
3187, 3061, 2970, 2871, 1714, 1691, 1660, 1639, 1603, 1556, 1495, 1468, 1455, 1442, 1384, 1366, 1333, 1311,
1283, 1162, 1148, 1071, 1013, 883, 770, 733, 695. 1H-NMR ((D6)DMSO): 0.81, 0.88 (2d, 1:1, J ¼ 6.8,
Me2CH); 0.98, 0.99 (2d, 1:1, J ¼ 6.1, Me2CH); 1.76 (dsept., J ¼ 1.5, 6.6, Me2CH); 2.73 (t, J ¼ 5.1, HꢀC(5));
2.89 (sept., J ¼ 6.3, Me2CH); 3.44, 3.48 (2d, 1:1, J ¼ 13.8, CH2); 4.09 (dd, J ¼ 5.1, 7.8, HꢀC(4)); 7.20 – 7.33
(m, 5 arom. H); 8.69 (d, J ¼ 7.9, NH); 9.68 (s, HꢀN(2)). 13C-NMR ((D6)DMSO): 17.7; 18.0; 18.0; 20.8;
30.9; 42.0; 52.2; 55.8; 69.8; 126.3; 128.2; 128.9; 136.2; 169.4; 169.7. ESI-MS: 304 ([M þ H]þ). HR-ESI-
MS: 304.2017 ([M þ H]þ, C17H26N3Oþ2 ; calc. 304.2020). Anal. calc. for C17H25N3O2 · 1/8 H2O (305.65): C
66.80, H 8.33, N 13.75; found: C 66.61, H 8.45, N 13.85.
13.2. N-[(4RS,5RS)-1-Benzyl-2-methyl-3-oxo-5-(propan-2-yl)pyrazolidin-4-yl]-2-phenylacetamide
(19). Prepared from 15a (257 mg, 1.04 mmol). Yield: 288 mg (82%). Yellow solid. M.p. 141 – 1458. IR
(KBr): 3260, 3206, 3060, 3031, 2960, 2928, 2870, 1660, 1603, 1585, 1543, 1494, 1464, 1454, 1429, 1405, 1386,
1368, 1355, 1343, 1332, 1311, 1296, 1282, 1215, 1160, 1127, 1099, 1064, 1030, 1005, 982, 930, 918, 899, 845,
808, 753, 731, 718, 698, 671, 623, 611. 1H-NMR (CDCl3): 0.80, 0.82 (2d, 1:1, J ¼ 6.8, Me2CH); 1.76 (dsept.,
J ¼ 1.6, 6.8, Me2CH); 2.85 (dd, J ¼ 2.5, 5.1, HꢀC(5)); 3.03 (s, Me); 3.35, 3.39 (2d, 1:1, J ¼ 19.0, CH2); 3.81,
3.86 (2d, 1:1, J ¼ 13.6, CH2); 4.18 (dd, J ¼ 2.4, 7.1, HꢀC(4)); 5.11 (d, J ¼ 7.0, NH); 7.10 – 7.14, 7.21 – 7.38
(2m, 1:4, 10 arom. H). 13C-NMR (CDCl3): 17.3; 18.9; 30.5; 32.1; 43.4; 54.7; 60.5; 69.8; 127.4; 128.4; 128.8;
129.0; 129.4; 130.4; 134.8; 135.4; 168.8; 170.7. ESI-MS: 366 ([M þ H]þ). HR-ESI-MS: 366.2175 ([M þ
H]þ, C22H28N3Oþ2 ; calc. 366.2176). Anal. calc. for C22H27N3O2 · 1/6 H2O (368.47): C 72.30, H 7.45, N
11.50; found: C 71.96, H 7.47, N 11.49.
12. X-Ray Crystal-Structure Analysis of Compounds 9k, 10f, and 12e (Figs. 3 – 5 and Table 4)3). For
X-ray crystal-structure determination, the crystals of the compounds 9k, 10f, and 12e were mounted on
the tip of glass fibres and transferred to the goniometer head. Diffraction data for 10f were collected on a
Nonius Kappa CCD diffractometer using monochromated MoKa radiation at 150 K by using Nonius
Collect software [32]. Data reduction and integration were performed with the software package
DENZO-SMN [33]. Diffraction data for 9k and 12e were collected on SuperNova X-ray single-crystal
diffractometer equipped with Atlas detector using monochromated MoKa radiation at r.t.; in this case,
the data reduction and integration were performed with the software package CrysAlis PRO [34]. The
coordinates of all of the non-H-atoms were found via direct methods using the SIR97 or Superflip
structure solution programs [35][36]. A full-matrix least-squares refinement on F2 magnitudes with
anisotropic displacement parameters for all non-H-atoms using SHELXL-97 was employed [37]. All H-
atoms were initially located in difference Fourier maps. All H-atoms attached to C-atom were
subsequently treated as riding atoms in geometrically idealized positions with CꢀH bond lengths of
0.96 ꢅ for Me, 0.97 ꢅ for CH2, 0.98 ꢅ for CH, and 0.93 ꢅ for aromatic CꢀH bonds. The corresponding
displacement parameters Uiso(H) were 1.5-times higher than those of the carrier Me C-atoms and 1.2-
times higher than all other H-bearing C-atoms. H-Atoms attached to N-atoms and (possibly) taking part
in H-bonding were found in the difference electron-density maps and refined isotropically with the
constraint Uiso(H) ¼ 1.2 Uiso(N). When the obtained NꢀH distances were too long, the appropriate bond
length restraints were used (NꢀH with lengths of 0.87(2) ꢅ). Crystal data, data collection, and structure
refinement for compounds 9k, 10f, and 12e are compiled in Table 4. Figures depicting the structures were
drawn by ORTEP3 [38].
3
)
CCDC-930454 – 930456 contain the supplementary crystallographic data for 9k, 10f, and 12e, resp.
These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.

266
Helvetica Chimica Acta – Vol. 97 (2014)
Table 4. Crystallographic Data for Compounds 9k, 10f, and 18
9k
10f
18
Empirical formula
Mr
C20H20N4O5
396.40
C20H23N3O3
353.41
C22H27N3O2
365.47
Crystal habit, color
Crystal system
Crystal dimensions [mm]
Temp. [K]
prism, colorless
monoclinic
0.30 ꢂ 0.15 ꢂ 0.10
150(2)
platelet, colorless
monoclinic
0.50 ꢂ 0.25 ꢂ 0.02
150(2)
prism, colorless
monoclinic
0.30 ꢂ 0.15 ꢂ 0.10
293(2)
Space group
P121/n 1
P121/c 1
C12/c 1
Z
4
4
8
Unit cell parameters:
a [ꢅ]
b [ꢅ]
c [ꢅ]
15.5657(5)
8.2240(2)
15.9538(5)
110.316(4)
1915.24(10)
1.375
11.3943(2)
18.5977(4)
9.6578(2)
112.2710(10)
1893.89(7)
1.239
28.3750(7)
8.8964(2)
16.2347(4)
90.413(2)
4098.11(17)
1.185
b [8]
V [ꢅ3]
Dx (Mg mꢀ3
)
Radiation type
MoKa
0.101
MoKa
0.085
MoKa
0.077
m [mmꢀ1
]
Diffractometer
SuperNova, Dual,
Cu at zero, Atlas
w
Nonius Kappa CCD
SuperNova, Dual,
Cu at zero, Atlas
w
Scan type
w
Absorption correction
Total reflections measured
Independent reflections
Observed reflections
Criterion for obs.
reflections
multi-scan
11172
4394
3331
F2 > 2.0 s(F2)
multi-scan
34551
4349
3215
F2 > 2.0 s(F2)
multi-scan
19555
4705
3419
F2 > 2.0 s(F2)
Rint
0.0281
0.045
0.0283
q Range [8]
h Range
k Range
l Range
Refinement on
R (on Fobs), wR (on Fobs), S
Total contributing
reflections
2.83 – 27.48
ꢀ 20 – 12
ꢀ 10 – 10
ꢀ 20 – 20
F2
1.93 – 27.51
ꢀ 14 – 14
ꢀ 24 – 24
ꢀ 12 – 12
F2
2.87 – 27.48
ꢀ 36 – 36
ꢀ 11 – 11
ꢀ 21 – 21
F2
0.0457, 0.1118, 1.030
4394
0.0579, 0.1451, 1.150
4349
0.0574, 0.1552, 1.039
4705
No. of parameters
H-Atom treatment
268
246
251
C-bonded treated
as riding, N-bonded
refined isotropically
< 0.001; < 0.001
0.251; ꢀ 0.209
C-bonded treated
as riding, N-bonded
refined isotropically
< 0.001; < 0.001
0.530; ꢀ 0.499
C-bonded treated
as riding, N-bonded
refined isotropically
< 0.001; < 0.001
0.319; ꢀ 0.242
(D/s)max; (D/s)ave
1max; 1min [eꢅꢀ3
]
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Helvetica Chimica Acta – Vol. 97 (2014)
267
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Received April 22, 2013