Reaction between 4-oxoalkane-1,1,2,2-tetracarbonitriles and morpholine: Regioselective synthesis of 5-amino-2-(morpholin-4-yl)-3-(2-oxoalkyl)-3H-pyr- rol-3,4-dicarbonitriles

Article abstract of DOI:10.1016/j.tetlet.2011.09.084

A new approach to the regioselective synthesis of polyfunctional 3H-pyrroles from 4-oxoalkane-1,1,2, 2-tetracarbonitriles is described. 5-Amino-3-(2-aryl-2-oxoethyl)-3H-pyrrol-3,4-dicarbonitriles are prepared from 4-aryl-4-oxobutane-1,1,2,2-tetracarbonitr

Full text of DOI:10.1016/j.tetlet.2011.09.084

Tetrahedron Letters 52 (2011) 6407–6410
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Reaction between 4-oxoalkane-1,1,2,2-tetracarbonitriles and morpholine:
regioselective synthesis of 5-amino-2-(morpholin-4-yl)-3-(2-oxoalkyl)-3H-pyr-
rol-3,4-dicarbonitriles
M. Yu. Belikov a, , O.V. Ershov a, A.V. Eremkin a, O.E. Nasakin a, V.A. Tafeenko b, E.V. Nurieva b
⇑
a Ulyanov Chuvash State University, Cheboksary, Moskovsky pr. 15, Russia
b Lomonosov Moscow State University, Moscow, Leninskie gori 1, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 July 2011
Revised 26 August 2011
Accepted 16 September 2011
Available online 24 September 2011
A new approach to the regioselective synthesis of polyfunctional 3H-pyrroles from 4-oxoalkane-1,1,2,
2-tetracarbonitriles is described. 5-Amino-3-(2-aryl-2-oxoethyl)-3H-pyrrol-3,4-dicarbonitriles are
prepared from 4-aryl-4-oxobutane-1,1,2,2-tetracarbonitriles. Diastereomeric 5-amino-2-morpholin-4-
yl-3-(2-oxocyclohexyl)-3H-pyrrole-3,4-dicarbonitriles were obtained from 1-(2-oxocyclohexyl)ethane-
1,1,2,2-tetracarbonitriles.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
4-Oxoalkane-1,1,2,2-tetracarbonitriles
3H-Pyrroles
Cyano groups
Deactivation
Being multifunctional compounds 4-oxoalkane-1,1,2,2-tetracar-
bonitriles1 contain competitive reaction centers that enable them to
take part in cascade transformations resulting in various classes of
heterocyclic compounds. It has been reported that reactions of
4-oxoalkane-1,1,2,2-tetracarbonitriles with nitrogen-containing
nucleophiles lead to amino-1,2-dicyano-4,6-diazabicyclo[3.2.1]
oct-2-en-7-ones,2a 3-amidinio-2-aminopyridine-4-carboxylates,2b
4-aryl-1,1,2-tricyano-4-oxobut-2-en-1-ides,2c 3,4-dicyano-5,6,7,8-
tetrahydroquinolin-2-olates,2d and cyclopenta[b]pyridines.2e Thus
the regioselectivity of these processes depends on the reaction con-
ditions and the nature of the initial compounds.
Vicinal cyano groups are the structural characteristics of 4-
oxoalkane-1,1,2,2-tetracarbonitriles, which can take part in the
formation of a pyrrole ring. In the case of systems with three sub-
stituents and one hydrogen atom a 3H-pyrrole ring should result.
Several synthetic methods for the preparation of 3H-pyrroles
are known: cyclization of open-chain compounds,3a–i 1,3-dipolar
cycloaddition,3j transformations of pyrrolidines,3k–n and anion-
radical reactions.3o,p Some 3H-pyrroles were shown to exhibit
antimicrobial or anticancer activity,4 therefore the search for new
efficient methods for their preparation is important.
5-amino-2-(morpholin-4-yl)-3-[2-oxoalkyl(cycloalkyl)]-3H-pyr-
rol-3,4-dicarbonitriles 2a–f (Scheme 1, Table 1) in 79–93% yield.5
The structures of compounds 2a–f were confirmed by IR, 1H and
13C NMR spectroscopy and by mass spectrometry.6 In the infrared
spectra the intense stretching absorptions due to the carbonyl
group were apparent at 1667–1691 cmÀ1 (for 2a–d) and 1720–
1723 cmÀ1 (for 2e,f). The absorption band of the conjugated cyano
group occurred at 2169–2182 cmÀ1, the nonconjugated cyano
group at 2230–2234 cmÀ1 and the amino group at 3149–3403 cm
À1. The 1H NMR spectra showed specific chemical shifts for the pro-
tons of the amino group at 7.19–7.28 ppm and the morpholine
fragment at 3.50–3.85 ppm. The morpholine protons appeared as
typically broadened signals, especially for derivatives 2e,f, while
the corresponding resonances of compounds 2a–d were only mod-
erately broad. The appearance of the 1H NMR signals can be
explained by hindered rotation of the morpholine fragment, which
is most evident in compounds 2e,f due to the spatial arrangement
of two sterically bulky substituents—the morpholine and cyclo-
hexyl groups. The diastereotopic methylene protons adjacent to
the C@O group in compounds 2a–c appeared as two doublets with
2Jgem = 17.7–17.8 Hz (AB spin system). The protons in compounds
2e,f appeared as double signals due to the formation of a diastereo-
meric mixture with chiral centers at the R2-group and nonconju-
gated b-CN group. The 1H NMR spectrum of compound 2e at
75 °C confirmed the presence of the diastereomeric pair, but at ele-
vated temperature the signals of the morpholine protons were
sharp and no longer broad. It should be mentioned that the
Morpholine was employed as the nucleophilic reagent and the
reaction of tetracarbonitriles 1a–f proceeded to give exclusively,
⇑
Corresponding author. Tel.: +7 9083002657; fax: +7 8352770979.
E-mail address: belikovmil@mail.ru (M. Yu. Belikov).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.09.084

6408
M. Yu. Belikov et al. / Tetrahedron Letters 52 (2011) 6407–6410
R1
R1
R1
R2
R2
NH
R2
NH
O
CN
O
CN
H
O
O
CN
O
NC
N
NC
NC
NC
CN
NH2
N
H2N
N
N
O
O
1a-f
Scheme 1. Synthesis of 3H-pyrroles 2a–f.
3a-f
2a-f
Table 1
Synthesis of 5-amino-2-morpholin-4-yl-3-[2-oxoalkyl(cycloalkyl)]-3H-pyrrol-3,4-
dicarbonitriles 2a–f
Carbonyl compound
R1
R2
Product
Yielda (%)
1a
1b
1c
1d
1e
1f
C6H5
H
H
H
CH3
2a
2b
2c
2d
2e
2f
93
85
91
79
88
81
4-ClC6H4
4-C6H5C6H4
4-CH3OC6H4
–(CH2)4–
–CH2CH2CH(t-Bu)CH2–
a
Yield of isolated product.
methine proton adjacent to the C@O group in compounds 2e,f oc-
curred as a doublet of doublets with 3J = 5.3–5.5 and 12.6–13.0 Hz
indicating its axial orientation. In the 13C NMR spectrum of com-
pound 2a the two cyano and carbonyl carbon atoms exhibited res-
onances at 117.56, 118.54, and 194.10 ppm, respectively, while the
carbons neighboring the nitrogen atom in the 3H-pyrrole ring were
detected as signals at 170.66 and 170.94 ppm. The mass spectra of
all the products exhibited base peaks (m/z = 216) corresponding to
the pyrrole fragment, while the molecular ion peaks had intensities
in the range 3–72%.
Figure 1. ORTEP diagram of compound 2a.
An unambiguous determination of the position of the morpho-
line group was achieved by X-ray diffraction analysis using a single
crystal of compound 2a (Fig. 1).7 The lone electron pair of nitrogen
salts with metal cations.8 The negative charge on these salts is
obviously delocalized on the dicyanomethine fragment and re-
duces the electrophilic properties of the terminal cyano groups,
which are thereby deactivated. This is the reason why 3H-pyrroles
3 do not form.
N5 conjugates with the p-system of the chain C2–N1–C5–N2, (the
distance N5–C2 is 1.329(3) Å and C2–N1 is 1.310(3) Å) despite the
repulsion of atoms H17aÁ Á ÁH8a (the distance H17aÁ Á ÁH8a is
2.10(3) Å, which is much less than the sum of the van der Waals
radii of the hydrogen atoms). This latter fact indicates the essential
difficulties associated with the substitution of H8a by any other
functional group. In the crystal state, molecules form centrosym-
metric dimers because of the N2–H2Á Á ÁN3i (i-symmetry code:
1Àx, Ày, Àz;) hydrogen bonds.
Tetracyanoalkanone derivatives are able to transform into com-
pounds with an iminofuran fragment under basic conditions, for
example, in reactions with sodium borohydride2f or pyridine.2g
Therefore, we assume that ketonitrile salts A transform into imin-
ofuran derivatives B. The reaction of amines with imino esters is an
example of Pinner amidine synthesis,9 and proceeds via addition to
the imine fragment and leads to intermediate C. The next stage is
the formation of pyrrole D. The synthesis of structurally analogous
furo[2,3-b]pyrroles had earlier been realized from tetracyanoalk-
anes by the treatment with sodium borohydride.2f Finally the
intermediate D undergoes ring-opening of the furan moiety with
the formation of E, which is further transformed into product 2.
To prove the formation of 3H-pyrroles 2 proceeds through the
intermediate B we synthesized its structural analog, 12-imino-9-
phenyl-10,11-dioxatricyclo[5.3.2.01,6]dodecane-7,8,8-tricarbonitri-
le 42h and treated it with morpholine under similar conditions. The
reaction resulted in 5-amino-2-(morpholin-4-yl)-3-(2-oxocyclo-
hexyl)-3H-pyrrol-3,4-dicarbonitrile (2e) (Scheme 3) in 82% yield.
In conclusion, an example of a new synthetic method for the
preparation of polyfunctional 3H-pyrroles via cyclization of vicinal
dinitrile-containing compounds has been demonstrated. The sim-
plicity, high yields, and regiospecificity of the procedure described
make it attractive for further investigation. The scope of this chem-
istry will be investigated by the variation of the initial nitriles and
nucleophilic components.
The preparation of aryl-containing 3H-pyrroles 2a–d was car-
ried out at reduced temperature in ethyl acetate over 2–3 days,
while the synthesis of compounds 2e,f took 10–20 min in a solu-
tion of water and 2-propanol (10:1 by volume).
It is significant to note that all the mentioned reactions led
exclusively to 3H-pyrroles 2, but not to regioisomeric derivatives
3. On the basis of this result, we assume that attack of the suffi-
ciently bulky morpholine nucleophile is directed toward one of
the b-cyano groups instead of the more sterically accessible termi-
nal cyano groups. In the substrates the b-cyano groups are
surrounded by two bulky fragments, the carbonyl, and dicyanom-
ethyl groups, therefore direct attack of morpholine is very difficult.
Keeping this fact in mind the following inferences can be made: (1)
the terminal cyano groups are deactivated; (2) the carbonyl group
takes part in the transformations. A possible mechanism for this
transformation is depicted in Scheme 2.
In the first stage, morpholine possibly acts as a base and forms a
salt with the CH-acidic center of the substrate. Previously the syn-
thesis of similar salts with ammonia had been carried out in ethyl
acetate.2c It is also known that tetracyanoalkanes are able to form

M. Yu. Belikov et al. / Tetrahedron Letters 52 (2011) 6407–6410
CN CN
6409
CN
NC
NC
NC
NH
NH
R2
R2
R1
R2
R1
CN
CN
NH
CN
O
O
1
CN
NH2
O
+
NH2
R1
O
O
N
O
O
А
B
C
NC
O
NC
NH2
NH2
+
NC
NC
NH2
R2
R1
R2
R1
O
N
N
2
NH
N
N
O
O
O
O
E
D
Scheme 2. A possible mechanism for the formation of 3H-pyrroles 2.
NC
CN
CN
NH2
NC
NC
NC
CN
NH
R2
R1
CN
NH
O
N
Ph
NH
- PhC(O)H
O
O
N
O
O
4
2e
B
O
Scheme 3. Cross-synthesis of 3H-pyrrole 2e.
49–52; (c) Padmavathi, V.; Radha, L. T.; Mahesh, K.; Padmaja, A. A. Chem. Pharm.
Bull. 2009, 57, 1200–1205.
Acknowledgment
5. Typical procedure for the preparation of 5-amino-2-morpholin-4-yl-3-(2-aryl-2-
oxo)-3H-pyrrole-3,4-dicarbonitriles 2a–d. To a stirred solution of the appropriate
4-aryl-4-oxobutane-1,1,2,2-tetracarbonitrile 1a–d (0.5 mmol) in dry EtOAc
(3 ml) at À5 to À10 °C was added morpholine (1 mmol) and the reaction
mixture became yellow-orange in color. After 2–3 d at À5 to À10 °C the
precipitated light-yellow solid was filtered, washed sequentially with cold
EtOAc (2 ml) and Et2O (1 ml) and dried. Typical procedure for the preparation of 5-
amino-2-morpholin-4-yl-3-(2-oxocyclohexyl)-3H-pyrrole-3,4-dicarbonitriles 2e,f.
To a stirred suspension of the appropriate 1-(2-oxocyclohexyl)ethane-1,1,2,2-
tetracarbonitrile 1e,f (0.5 mmol) in a 10:1 mixture of H2O and iPrOH (5 ml) was
added morpholine (1 mmol) and the reaction mixture became transparent yellow
in color. After stirring at room temperature for 15–30 min the newly precipitated
solid was filtered, washed sequentially with H2O (5 ml) and iPrOH (2 ml). The
isolated products were purified by crystallization from iPrOH and dried.
6. Analytical data for compounds 2a–f. Compound 2a. mp 208–209 °C; 1H NMR
This research was supported by the Federal Target Program
(Reseach and educational personnel of innovative Russia) as
research project (No 16.740.11.0160).
References and notes
1. (a) Middleton, W. J.; Heckert, R. E.; Little, E. L.; Krespas, C. G. J. Am. Chem. Soc.
1958, 80, 2783–2788; (b) Nikolaev, E. G.; Nasakin, O. E.; Terent’ev, P. B.; Khaskin,
B. A.; Petrov, V. G. Zh. Org. Khim. 1984, 20, 205–206.
2. (a) Nasakin, O. E.; Sheverdov, V. P.; Ershov, O. V.; Moiseeva, I. V.; Lyshchikov, A.
N.; Khrustalev, V. N.; Yu Antipin, M. Mendeleev Commun. 1997, 7, 112–113; (b)
Nasakin, O. E.; Sheverdov, V. P.; Moiseeva, I. V.; Lyshchikov, A. N.; Ershov, O. V.;
Nesterov, V. N. Tetrahedron Lett. 1997, 38, 4455–4456; (c) Yu Belikov, M.; Ershov,
O. V.; Eremkin, A. V.; Kayukov, Ya. S.; Nasakin, O. E. Zh. Org. Khim. 2010, 46, 604–
605 (Russ. J. Org. Chem. 2010, 46, 597–598); (d) Yu Belikov, M.; Ershov, O. V.;
Eremkin, A. V.; Kayukov, Ya. S.; Nasakin, O. E. Zh. Org. Khim. 2010, 46, 621–622
(Russ. J. Org. Chem. 2010, 46, 615–616); (e) Takehana, T.; Shimizu, K.; Yokozawa,
T.; Kimura, T.; Nishikata, A. Tetrahedron Lett. 1999, 40, 4707–4710; (f) Nasakin,
O. E.; Sheverdov, V. P.; Moiseeva, I. V.; Lyshchikov, A. N.; Ershov, O. V.;
Chernushkin, A. N.; Nesterov, V. N. Zh. Obsch. Khim. 1999, 69, 302–311; (g)
Ducker, J. M.; Gunter, M. J. Aust. J. Chem. 1973, 26, 1551–1569; (h) Nasakin, O. E.;
Lyshchikov, A. N.; Kayukov, Ya S.; Sheverdov, V. P. Pharm. Chem. J. 2000, 34, 170–
185.
3. (a) Ichikawa, J.; Sakoda, K.; Mihara, J.; Ito, N. J. Fluorine Chem. 2006, 127, 489–
504; (b) Svilarich-Soenen, M.; Foucaud, A. Tetrahedron 1972, 28, 5149–5155; (c)
Korostova, S. E.; Schevchenko, S. G.; Sigalov, M. V. Chem. Heterocycl. Compd.
1991, 27, 1101–1104; (d) Depature, M.; Grimaldi, Ja.; Hatem, Ja. Eur. J. Org. Chem
2001, 941–946; (e) Soufyane, M.; Mirand, C.; Lévy, J. Tetrahedron Lett. 1993, 34,
7737–7740; (f) Lui, K. H.; Sammes, M. P. J. Chem. Soc., Perkin Trans. 1 1990, 457–
468; (g) Chiu, P. K.; Lai, T. P.; Sammes, M. P. J. Chem. Res. (M). 1990, 428–439; (h)
Merot, P.; Gadreau, C.; Foucaud, A. Tetrahedron 1981, 37, 2595–2599; (i)
Foucaud, A.; Leblanc, R. Tetrahedron Lett. 1969, 10, 509–512; (j) Firestone, R. A.
Tetrahedron 1977, 33, 3009–3039; (k) McEwen, W. E.; Yee, T. T.; Liao, T. K.; Wolf,
A. P. J. Org. Chem. 1967, 32, 1947–1954; (l) Jacobi, P. A.; Liu, H. J. Am. Chem. Soc.
1999, 121, 1958–1959; (m) Chiu, P.-H.; Sammes, M. P. Tetrahedron 1990, 46,
3439–3456; (n) Schmitt, G.; Nasser, B.; Dinh, N.; Laude, B.; Roche, M. Can. J.
Chem. 1990, 68, 863–868; (o) Xu, X.; Zhang, Y. Synth. Commun. 2002, 32, 2643–
2650; (p) Xu, X.; Zhang, Y. J. Chem. Soc., Perkin Trans. 1 2001, 2836–2839.
4. (a) Cirrincione, G.; Almerico, A. M.; Dattolo, G.; Aiello, E.; Grimaudo, S.; Diana, P.;
Misuraca, F. Farmaco 1992, 47, 1555–1562; (b) Cirrincione, G.; Almerico, A. M.;
Grimaudo, S.; Diana, P.; Mingoia, F.; Barraja, P.; Misuraca, F. Farmaco 1996, 51,
(500.13 MHz, DMSO-d6):
d 3.62–3.80 (8H, m, morpholine), 3.92 (1H, d,
J = 17.8 Hz, CH2CO), 4.06 (1H, d, J = 17.8 Hz, CH2CO), 7.27 (2H, s, NH2), 7.53–
7.57 (2H, m, 2-m-H-Ar), 7.67–7.70 (1H, m, 1-p-H-Ar), 7.98–8.01 (2H, m, 2-o-H-
Ar). 13C NMR (125.76 MHz, DMSO-d6): d 42.73, 47.45, 57.54, 65.98, 117.56,
118.54, 128.66, 129.17, 134.24, 136.17, 170.66, 170.94, 194.10. IR (mineral oil,
cmÀ1) 3184–3311 (NH2), 2232, 2182 (C„N), 1691 (C@O). MS (EI, 70 eV): m/z (%)
335 (M+, 72), 216 (100). Anal. Calcd for C18H17N5O2: C, 64.47; H, 5.11; N, 20.88.
Found: C, 64.57; H, 5.02; N, 20.97. Compound 2b. mp 220–221 °C; 1H NMR
(500.13 MHz, DMSO-d6):
d 3.66–3.78 (8H, m, morpholine), 3.90 (1H, d,
J = 17.7 Hz, CH2CO), 4.06 (1H, d, J = 17.7 Hz, CH2CO), 7.26 (2H, s, NH2), 7.61–
7.64 (2H, m, H3,5-Ar), 7.99–8.03 (2H, m, H2,6-Ar). IR (mineral oil, cmÀ1) 3157–
3403 (NH2), 2233, 2172 (C„N), 1667 (C@O). MS (EI, 70 eV): m/z (%) 369 (M+, 3),
216 (100). Anal. Calcd for C18H16ClN5O2: C, 58.46; H, 4.36; N, 18.94. Found: C,
58.53; H, 4.31; N, 19.02. Compound 2c. mp 229–230 °C; 1H NMR (500.13 MHz,
DMSO-d6): d 3.67–3.79 (8H, m, morpholine), 3.96 (1H, d, J = 17.7 Hz, CH2CO),
4.10 (1H, d, J = 17.7 Hz, CH2CO), 7.29 (2H, s, NH2), 7.43–7.46 (1H, m, Ar), 7.50–
7.54 (2H, m, Ar), 7.74–7.79 (2H, m, Ar), 7.82–7.87 (2H, m, Ar), 8.04–8.10 (2H, m,
Ar). IR (mineral oil, cmÀ1) 3167–3401 (NH2), 2234, 2179 (C„N), 1668 (C@O). MS
(EI, 70 eV): m/z (%) 411 (M+, 3), 216 (100). Anal. Calcd for C24H21N5O2: C, 70.06;
H, 5.14; N, 17.02. Found: C, 69.89; H, 5.18; N, 17.13. Compound 2d. mp 211–
212 °C; 1H NMR (500.13 MHz, DMSO-d6): d 0.98 (3H, d, J = 6.9 Hz, CH3), 3.68–
3.76 (8H, m, morpholine), 3.86 (3H, s, OCH3), 4.26 (1H, q, J = 6.9 Hz, CHCH3), 7.08
(2H, d, J = 8.9 Hz, H3,5-Ar), 7.28 (2H, s, NH2), 8.00 (2H, d, J = 8.9 Hz, H2,6-Ar). IR
(mineral oil, cmÀ1) 3149–3347 (NH2), 2233, 2169 (C„N), 1672 (C@O). MS (EI,
70 eV): m/z (%) 379 (M+, 5), 216 (100). Anal. Calcd for C20H21N5O3: C, 63.31; H,
5.58; N, 18.46. Found: C, 63.33; H, 5.51; N, 18.52. Compound 2e. mp 195–196 °C;
1H NMR (500.13 MHz, DMSO-d6): d 1.24–2.42 (8H, m, 4CH2), 3.43 (1H, dd,
J = 5.5, 12.6 Hz CHCO); 3.50–3.85 (8H, m, morpholine), 7.19⁄, 7.27 (2H, s, NH2).
1H NMR (500.13 MHz, DMSO-d6, 348 K): d 1.28–2.38 (8H, m, 4CH2), 3.37 (1H, dd,

6410
M. Yu. Belikov et al. / Tetrahedron Letters 52 (2011) 6407–6410
J = 5.7, 12.5 Hz CHCO), 3.50 (1H, dd, J = 5.6, 12.4 Hz CHCO), 3.60–3.80 (8H, m,
7. Crystallographic data (excluding structure factors) for the structure 2a in this
paper have been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 804729. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge, CB2
1EZ, UK [fax: +44 (0) 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk].
8. (a) Carlucci, L.; Ciani, G.; Proserpio, D. M.; Sironi, A. Angew. Chem., Int. Ed. 1996,
35, 1088–1090; (b) Nasakin, O. E.; Nikolaev, E. G.; Terent’ev, P. B.; Sheludyakov,
V. D. Zh. Org. Khim. 1987, 23, 659–660.
morpholine), 6.86⁄, 6.95 (2H, s, NH2). IR (mineral oil, cmÀ1) 3174–3324 (NH2),
2230, 2174 (C„N), 1719 (C@O). MS (EI, 70 eV): m/z (%) 313 (M+, 24), 216 (100).
Anal. Calcd for C16H19N5O2: C, 61.33; H, 6.11; N, 22.35. Found: C, 61.45; H, 6.02;
N, 22.42. Compound 2f. mp 125–126 °C; 1H NMR (500.13 MHz, DMSO-d6): d 0.91,
0.93⁄ (9H, s, t-Bu), 1.05–2.80 (7H, m, 3CH2+CH), 3.47 (1H, dd, J = 5.3, 13.0 Hz,
CHCO), 3.55–3.80 (8H, m, morpholine), 7.20, 7.26⁄ (2H, s, NH2). IR (mineral oil,
cmÀ1) 3183–3354 (NH2), 2234, 2179 (C„N), 1723 (C@O). MS (EI, 70 eV): m/z (%)
369 (M+, 3), 216 (100). Anal. Calcd for C20H27N5O2: C, 65.02; H, 7.37; N, 18.96.
Found: C, 65.11; H, 7.30; N, 19.01; ⁄refers to signals of the diastereoisomers.
9. (a) Roger, R.; Neilson, D. G. Chem. Rev. 1961, 61, 179–211; (b) Shriner, R. L.;
Neumann, F. W. Chem. Rev. 1944, 35, 351–425.