Synthesis of N,N′-di(tert-butyl)bispidin-9-ones

Article abstract of DOI:10.1007/s11172-012-0043-4

Condensation of 1,3,5-tri(tert-butyl)-1,3,5-triazacyclohexane with acetone gave 3,7-di(tert-butyl)-1,5-bis[(tert-butylamino)methyl]bispidin-9-one. Reactions with ethyl methyl ketone and other ketones of the formula RCH ₂COCH₃ yielded

Full text of DOI:10.1007/s11172-012-0043-4

Russian Chemical Bulletin, International Edition, Vol. 61, No. 2, pp. 308—312, February, 2012
308
Synthesis of N,N´ꢀdi(tertꢀbutyl)bispidinꢀ9ꢀones
A. I. Kuznetsov,a I. M. Senan,a and T. M. Serovab
aM. V. Lomonosov Moscow State University of Fine Chemical Technologies,
86 prosp. Vernadskogo, 119571 Moscow, Russian Federation.
Eꢀmail: tetraza@mail.ru
bInstitute of Physiologically Active Compounds, Russian Academy of Sciences,
Chernogolovka, Moscow Region, Russian Federation.
Eꢀmail: serova@ipac.ac.ru
Condensation of 1,3,5ꢀtri(tertꢀbutyl)ꢀ1,3,5ꢀtriazacyclohexane with acetone gave 3,7ꢀdi(tertꢀ
butyl)ꢀ1,5ꢀbis[(tertꢀbutylamino)methyl]bispidinꢀ9ꢀone. Reactions with ethyl methyl ketone and
other ketones of the formula RCH2COCH3 yielded 5ꢀRꢀ3,7ꢀdi(tertꢀbutyl)ꢀ1ꢀ[(tertꢀbutylꢀ
amino)methyl]bispidinꢀ9ꢀones, while reactions with diethyl ketone and other symmetrical
ketones of the formula RCH2COCH2R afforded 1,5ꢀRꢀ3,7ꢀdi(tertꢀbutyl)bispidinꢀ9ꢀones.
Key words: bispidine, 3,7ꢀdiazabicyclo[3.3.1]nonane, condensation, acetone, ethyl methyl
ketone, diethyl ketone, 1,3,5ꢀtri(tertꢀbutyl)ꢀ1,3,5ꢀtriazacyclohexane, 3,7ꢀdi(tertꢀbutyl)bispidinꢀ
9ꢀone derivatives, 3,7ꢀdi(tertꢀbutyl)ꢀ3,7ꢀdiazabicyclo[3.3.1]nonanꢀ9ꢀone derivatives.
Scheme 1
In recent years, researchers dealing with azaadamanꢀ
tane chemistry1 have experienced a renewal of interest in
structurally related 1,3ꢀdiazaadamantane (1,3ꢀdiazatriꢀ
cyclo[3.3.1.13,7]decane) and bispidine (3,7ꢀdiazabicycloꢀ
[3.3.1]nonane).2—4
This is explained by their various physiological activiꢀ
ty5,6 and the tendency of bispidine derivatives to form comꢀ
plexes7,8 with, e.g., transition metal salts. The most accesꢀ
sible bispidine derivatives are bispidinꢀ9ꢀones containing
substituents at the bridgehead atoms 1 and 5, which can be
prepared by condensation of ketones with formaldehyde
and primary amines according to the Mannich reaction
pattern (Scheme 1).
Scheme 2
Here we present the data for the transformation of
1,3,5ꢀtri(tertꢀbutyl)ꢀ1,3,5ꢀtriazacyclohexane9 (1) into
3,7ꢀdi(tertꢀbutyl)ꢀ3,7ꢀdiazabicyclo[3.3.1]nonanꢀ9ꢀones
(N,N´ꢀdi(tertꢀbutyl)bispidinꢀ9ꢀones) 2—5 by condensaꢀ
tion with acetone and other ketones. The tertꢀbutyl groups
were used as substituents at the N atoms because they can
subsequently be removed.10
By condensation of triazacyclohexane 1 with ketones
containing four acidic H atoms, we obtained 1,5ꢀdisubstiꢀ
tuted N,N´ꢀdi(tertꢀbutyl)bispidinꢀ9ꢀones 2a—e in 58—88%
yields (Scheme 2).
2: R = Me (a), Et (b), Pr (c), Bn (d), Ph (e)
The yield of dimethylbispidinone 2a was 72%; earliꢀ
er,11 this compound has been obtained by condensation of
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 307—311, February, 2012.
1066ꢀ5285/12/6102ꢀ308 © 2012 Springer Science+Business Media, Inc.

Synthesis of N,N´ꢀdi(tertꢀbutyl)bispidinꢀ9ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
309
Scheme 3
Scheme 4
diethyl ketone with tertꢀbutylamine and formaldehyde in
30% yield (see Scheme 1).
A possible mechanism of the reaction of 1,3,5ꢀtriazaꢀ
cyclohexanes with ketones is shown in Scheme 3.
In a first step, AcOH protonates triazacyclohexane to
give carbenium immonium cation A, which further reacts
with the starting ketone. The resulting adduct B elimiꢀ
nates methylenediamine molecule RHN—CH2—NHR
and is transformed through intermediate C into piperiꢀ
done D. Piperidone D reacts in a similar way with a secꢀ
ond triazacyclohexane molecule to give bispidinone E as
a final product. Scheme 3 displays only some of the possiꢀ
ble intermediates. The possibility of the intermediate forꢀ
mation of piperidone D was experimentally confirmed with
1ꢀtertꢀbutylꢀ3ꢀ[(tertꢀbutylamino)methyl]ꢀ5ꢀ(phenylthio)ꢀ
piperidinꢀ4ꢀone (3) as an example (Scheme 4).
We carried out the synthesis of bispidinones under difꢀ
ferent reaction conditions. nꢀButanol was used as a solꢀ
vent for compounds 2a—e. The highest yield of bispidinoꢀ
nes was achieved when the molar ratio of ketone : triazaꢀ
cyclohexane : AcOH was 1 : 1.3 : 2.8. Bispidinones 4a—d
and 5 were obtained in EtOH.
Scheme 5
Condensation of triazacyclohexane 1 with ketones conꢀ
taining five acidic H atoms (RCH2COCH3), gave earlier
unknown 5ꢀsubstituted N,N´ꢀdi(tertꢀbutyl)ꢀ1ꢀ[(tertꢀbutylꢀ
amino)methyl]bispidinꢀ9ꢀones 4a—d in 50—70% yields
(Scheme 5).
With acetone as the starting ketone, the condensation
involves all the six H atoms to form N,N´ꢀdi(tertꢀbutyl)ꢀ
1,5ꢀbis[(tertꢀbutylamino)methyl]bispidinꢀ9ꢀone (5) in
40% yield (Scheme 6).
The structures of compounds 2—5 were confirmed by
elemental analysis data and NMR and mass spectra.
To sum up, we developed an efficient method for the
synthesis of 1,5ꢀdisubstituted 3,7ꢀdi(tertꢀbutyl)ꢀ3,7ꢀdiazaꢀ
bicyclo[3.3.1]nonanꢀ9ꢀones (N,N´ꢀdi(tertꢀbutyl)bispidinꢀ
9ꢀones). The method involves condensation of acetone
4: R = Me (a), Bn (b), PhS (c), Me2C=CHCH2 (d)

310
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Kuznetsov et al.
Scheme 6
C(6), C(8)), 52.72 (3,7ꢀCN), 46.24 (C(1), C(5)), 26.23
(2 C(CH3)3), 20.22 (1,5ꢀMe). MS, m/z (Irel (%)): 280 [M]+ (49),
223 (48), 194 (65), 180 (82), 124 (100), 100 (89), 86 (74), 84 (45),
70 (85), 57 (81), 43 (37).
3,7ꢀDi(tertꢀbutyl)ꢀ1,5ꢀdiethylꢀ3,7ꢀdiazabicycloꢀ[3.3.1]nonanꢀ
9ꢀone (2b). Yield 9.00 g (58%), white crystals, m.p. 56—58 C
(from toluene). Found (%): C, 74.32; H, 11.96; N, 8.75.
C19H36N2O. Calculated (%): C, 73.97; H, 11.76; N, 9.08. IR,
/cm–1: 1720 (C=O). 1H NMR, : 0.88 (t, 6 H, 2 CH2CH3,
J = 7.3 Hz); 1.05 (s, 18 H, 2 Me3C); 1.42 (q, 4 H, 2 CH2Me,
J = 8.1 Hz); 2.50 (d, 4 H, 2 NCH2C, J = 10.3 Hz); 3.00 (d, 4 H,
2 NCH2C, J = 10.3 Hz). 13C NMR, : 217.18 (CO(9)), 56.35
(C(2), C(4), C(6), C(8)), 53.52 (3,7ꢀCN), 49.68 (C(1), C(5)),
26.65 (2 C(CH3)3), 26.59 (1,5ꢀCH2Me), 7.84 (1,5ꢀCH2CH3).
MS, m/z (Irel (%)): 308 [M]+ (22), 223 (71), 209 (34), 152 (100),
100 (77), 84 (19), 70 (18), 57 (83), 43 (77).
3,7ꢀDi(tertꢀbutyl)ꢀ1,5ꢀdipropylꢀ3,7ꢀdiazabicyclo[3.3.1]nonanꢀ
9ꢀone (2c). Yield 11.80 g (69%), white crystals, m.p. 86—88 C
(from toluene). Found (%): C, 75.46; H, 12.04; N, 8.14.
C21H40N2O. Calculated (%): C, 74.94; H, 11.98; N, 8.32. IR,
/cm–1: 1710 (C=O). 1H NMR, : 0.90 (s, 6 H, 2 CH2CH3);
1.05 (s, 18 H, 2 Me3C); 1.35 (s, 8 H, 2 CCH2CH2Me); 2.50
(d, 4 H, 2 NCH2C, J = 10.3 Hz); 3.00 (d, 4 H, 2 NCH2C,
J = 10.3 Hz). 13C NMR, : 217.22 (CO(9)), 56.77 (C(2), C(4),
C(6), C(8)), 53.49 (3,7ꢀCN), 49.71 (C(1), C(5)), 36.68
(1,5ꢀCH2Et), 26.60 (2 C(CH3)3), 16.66 (1,5ꢀCH2CH2Me), 15.22
(1,5ꢀ(CH2)2CH3). MS, m/z (Irel (%)): 336 [M]+ (25), 279 (22),
250 (54), 236 (83), 180 (94), 100 (100), 86 (24), 70 (23), 57 (46),
45 (53).
1,5ꢀDibenzylꢀ3,7ꢀdi(tertꢀbutyl)ꢀ3,7ꢀdiazabicyclo[3.3.1]nonanꢀ
9ꢀone (2d). Yield 16.24 g (75%), white crystals, m.p. 184—185 C
(from toluene). Found (%): C, 80.67; H, 9.27; N, 6.63.
C29H40N2O. Calculated (%): C, 80.51; H, 9.32; N, 6.47. IR,
/cm–1: 1715 (C=O), 1598 (Ar). 1H NMR, : 0.96 (s, 18 H,
2 Me3C); 2.76 (d, 4 H, 2 NCH2C, J = 10.0 Hz); 2.98 (d, 4 H,
2 NCH2C, J = 10.0 Hz); 2.90 (s, 4 H, 2 CCH2, Ar); 7.18—7.45
(m, 10 H, 2 Ar). MS, m/z (Irel (%)): 432 [M]+ (25), 375 (22), 332
(54), 248 (83), 100 (100), 91 (30), 77 (23), 57 (46), 43 (53).
3,7ꢀDi(tertꢀbutyl)ꢀ1,5ꢀdiphenylꢀ3,7ꢀdiazabicyclo[3.3.1]nonanꢀ
9ꢀone (2e). A solution of 1,3ꢀdiphenylpropanꢀ2ꢀone (10.51 g,
50 mmol), triazacyclohexane 1 (16.60 g, 65 mmol), and AcOH
(8.41 g, 140 mmol) in BunOH (20 mL) was gently refluxed for
2 h. The precipitate that formed was filtered off, washed with
PriOH (10 mL), and recrystallized from EtOH. The yield of
compound 2e was 17.71 g (88%), white crystals, m.p. 210—211 C
(from EtOH). Found (%): C, 79.99; H, 9.04; N, 7.16.
C27H36N2O. Calculated (%): C, 80.15; H, 8.97; N, 6.92. IR,
/cm–1: 1715 (C=O), 1595 (Ar). 1H NMR, : 1.14 (s, 18 H,
2 Me3C); 3.10 (d, 4 H, 2 NCH2C, J = 10.2 Hz); 3.59 (d, 4 H,
2 NCH2C, J = 10.2 Hz); 7.04—7.30 (m, 10 H, 2 Ar). 13C NMR,
: 211.36 (CO(9)), 143.83, 129.12, 127.45, 126.10 (2 Ph), 58.14
(C(2), C(4), C(6), C(8)), 54.71 (C(1), C(5)), 53.72 (3,7ꢀCN),
26.43 (2 C(CH3)3). MS, m/z (Irel (%)): 404 [M]+ (18), 347 (17),
318 (69), 304 (53), 248 (57), 132 (32), 100 (100), 91 (46), 77 (30),
57 (46), 43 (58).
and some other ketones with 1,3,5ꢀtri(tertꢀbutyl)ꢀ1,3,5ꢀ
triazacyclohexane 1.
Experimental
Domestic solvents and reagents (reagent grade) were used.
1ꢀ(Phenylthio)propanꢀ2ꢀone was prepared as described earliꢀ
er.12 IR spectra were recorded on a Bruker IFSv spectrophotoꢀ
meter in KBr pellets. 1H and 13C NMR spectra were recorded on
a Bruker AMꢀ300 spectrometer (300.13 (1H) and 75.47 MHz (13C))
in CDCl3 with SiMe4 as the internal standard. Mass spectra (EI)
were measured on an MSꢀ30 Kratos instrument (direct inlet
probe, ionization voltage 70 eV, ion source temperature 200 C).
Highꢀresolution mass spectra (ESI)13 were recorded on a Bruker
micrOTOF II instrument in the positive (capillary voltage 4500 V)
or negative ion mode (capillary voltage 3200 V). The m/z scan
range was 50—3000 Da; the instrument was calibrated externally
or internally (Electrospray Calibrant Solution, Fluka). Solutions
in acetonitrile, methanol, or water were syringed at a rate of
3 L min–1. Nitrogen was used as a spraying gas (4 L min–1); the
interface temperature was 180 C. Melting points were deterꢀ
mined on a PTPꢀM instrument.
1,5ꢀDisubstituted 3,7ꢀdi(tertꢀbutyl)ꢀ3,7ꢀdiazabicyclo[3.3.1]ꢀ
nonanꢀ9ꢀones 2a—d (general procedure). A solution of the keꢀ
tone RCH2COCH2R (50 mmol), triazacyclohexane 1 (16.60 g,
65 mmol), and AcOH (8.41 g, 140 mmol) in BunOH (25 mL)
was gently refluxed for 2 h. The reaction mixture was conꢀ
centrated and alkalified with K2CO3 to pH 10. The product
was extracted with boiling toluene (3Ч20 mL), the extract
was concentrated, and the residue was recrystallized from
toluene.
3,7ꢀDi(tertꢀbutyl)ꢀ1,5ꢀdimethylꢀ3,7ꢀdiazabicyclo[3.3.1]ꢀ
nonanꢀ9ꢀone (2a). Yield 10.10 g (72%), white crystals, m.p.
124—126 C (from toluene) (cf. Ref. 11: m.p. 128—130 C).
Found (%): C, 72.70; H, 11.38; N, 10.11. C17H32N2O. Calculatꢀ
ed (%): C, 72.81; H, 11.50; N, 9.99. IR, /cm–1: 1720 (C=O).
1H NMR, : 0.92 (s, 6 H, 2 Me); 1.01 (s, 18 H, 2 Me3C); 2.42
(d, 4 H, 2 NCH2C, J = 10.0 Hz); 3.00 (d, 4 H, 2 NCH2C,
J = 10.0 Hz). 13C NMR, : 216.20 (CO(9)), 58.41 (C(2), C(4),
1ꢀtertꢀButylꢀ3ꢀ[(tertꢀbutylamino)methyl]ꢀ5ꢀ(phenylthio)ꢀ
piperidinꢀ4ꢀone (3). A solution of 1ꢀ(phenylthio)propanꢀ2ꢀone
(1.66 g, 10 mmol), triazacyclohexane 1 (2.55 g, 10 mmol), and
AcOH (0.72 g, 12 mmol) in EtOH (20 mL) was refluxed for 6 h.
The reaction mixture was concentrated and alkalified with
K2CO3 to pH 10. The product was extracted with boiling toluene

Synthesis of N,N´ꢀdi(tertꢀbutyl)bispidinꢀ9ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
311
(3×10 mL). The extract was concentrated and the residue was
recrystallized from EtOH. The yield of compound 3 was 2.50 g
(72%), white crystals, m.p. 85—87 C (from EtOH). Found (%):
C, 68.97; H, 9.67; N, 8.10. C20H32N2OS. Calculated (%): C,
68.92; H, 9.25; N, 8.04. IR, /cm–1: 3327 (NH), 1715 (C=O),
580 (C—S). 1H NMR, : 1.05 (s, 18 H, 2 Me3CN); 1.92 (s, 1 H,
NH); 2.29 (s, 2 H, CH2NH); 2.31 (d, 2 H, NCH2, J = 9.5 Hz);
2.78 (d, 1 H, CH, J = 8.8 Hz); 3.40 (d, 2 H, NCH2C, J = 11.7 Hz);
4.00 (d, 1 H, CHS, J = 8.8 Hz); 7.27—7.41 (m, 5 H, Ar).
13C NMR, : 202.84 (CO), 136.92, 129.53, 129.11, 128.76 (SPh),
64.55 (2 CN), 57.67 (CHS), 53.89 (2 CH2N), 52.74 (CH2NH),
26.38 (2 C(CH3)3), 25.54 (CH). MS, m/z: found 349.2310
[M + H]+; C20H32N2OS; calculated M = 348.2235.
5ꢀSubstituted 3,7ꢀdi(tertꢀbutyl)ꢀ1ꢀ[(tertꢀbutylamino)methyl]ꢀ
3,7ꢀdiazabicyclo[3.3.1]nonanꢀ9ꢀones 4a—d (general procedure).
A solution of the ketone RCH2COCH3 (10 mmol), triazacycloꢀ
hexane 1 (5.11 g, 20 mmol), and AcOH (2.64 g, 44 mmol) in
EtOH (25 mL) was refluxed for 6 h. The reaction mixture was
concentrated and alkalified with K2CO3 to pH 10. The product
was extracted with boiling toluene (3Ч15 mL). The extract was
concentrated and the residue was recrystallized from EtOH.
3,7ꢀDi(tertꢀbutyl)ꢀ1ꢀ[(tertꢀbutylamino)methyl]ꢀ5ꢀmethylꢀ
3,7ꢀdiazabicyclo[3.3.1]nonanꢀ9ꢀone (4a). Yield 2.50 g (71%),
white crystals, m.p. 88—90 C (from EtOH). Found (%): C, 71.54;
H, 11.63; N, 12.03. C21H41N3O. Calculated (%): C, 71.74;
H, 11.75; N, 11.95. IR, /cm–1: 3405, 3318 (NH), 1711 (C=O).
1H NMR, : 0.92 (s, 3 H, Me); 1.00 (s, 9 H, (CH3)3CNH); 1.01
(s, 18 H, 2 Me3CN); 1.02 (s, 1 H, NH); 2.45 (s, 2 H, CCH2NH);
2.42 (d, 2 H, NCH2C, J = 10.3 Hz); 2.94 (d, 2 H, NCH2C,
J = 10.3 Hz); 2.72 (d, 2 H, NCH2C, J = 10.1 Hz); 3.02 (d, 2 H,
NCH2C, J = 10.1 Hz). 13C NMR, : 217.99 (CO(9)), 58.80
(C(4), C(6)), 55.52 (C(2), C(8)), 53.37 (3,7ꢀCN), 50.49 (CNH),
49.98 (CH2NH), 46.82 (C(5)), 46.04 (C(1)), 29.17 (NHC(CH3)3),
26.69 (2 C(CH3)3), 20.67 (5ꢀMe). MS, m/z: found 352.3318
[M + H]+; C21H41N3O; calculated M = 351.3450.
5ꢀBenzylꢀ3,7ꢀdi(tertꢀbutyl)ꢀ1ꢀ[(tertꢀbutylamino)methyl]ꢀ3,7ꢀ
diazabicyclo[3.3.1]nonanꢀ9ꢀone (4b). Yield 3.20 g (75%), white
crystals, m.p. 107—109 C (from EtOH). Found (%): C, 75.80;
H, 10.57; N, 9.36. C27H45N3O. Calculated (%): C, 75.83;
H, 10.61; N, 9.83. IR, /cm–1: 3333 (NH), 1711 (C=O).
1H NMR, : 0.95 (s, 18 H, 2 Me3CN); 1.02 (s, 9 H, (CH3)3CNH);
1.13 (s, 1 H, NH); 2.50 (s, 2 H, CCH2NH); 2.64 (d, 2 H,
NCH2C, J = 9.0 Hz); 2.90 (d, 2 H, NCH2C, J = 9.0 Hz); 2.76
(s, 2 H, CCH2Ar); 2.74 (d, 2 H, NCH2C, J = 8.7 Hz); 2.93 (d, 2 H,
NCH2C, J = 8.7 Hz); 7.09—7.24 (m, 5 H, Ar). 13C NMR, :
217.45 (CO(9)), 138.43, 130.89, 128.11, 126.14 (Ph), 56.03 (C(4),
C(6)), 55.62 (C(2), C(8)), 53.63 (3,7ꢀCN), 50.77 (CNH), 50.41
(CH2NH), 46.22 (C(5)), 46.04 (C(1)), 38.96 (1ꢀCH2Ph), 29.23
(NHC(CH3)3), 26.69 (2 C(CH3)3). MS, m/z: found 428.3614
[M + H]+; C27H45N3O; calculated M = 427.3562.
(3,7ꢀCN), 51.23 (CNH), 49.92 (CH2NH), 46.08 (C(1)), 29.08
(NHC(CH3)3), 26.58 (2 C(CH3)3). MS, m/z: found 446.3156
[M + H]+; C26H43N3OS; calculated M = 445.3127.
3,7ꢀDi(tertꢀbutyl)ꢀ1ꢀ[(tertꢀbutylamino)methyl]ꢀ5ꢀ(3ꢀmethylꢀ
butꢀ2ꢀenyl)ꢀ3,7ꢀdiazabicyclo[3.3.1]nonanꢀ9ꢀone (4d). Yield 2.80 g
(69%), white crystals, m.p. 122—123 C (from EtOH).
Found (%): C, 73.76; H, 11.35; N, 10.25. C25H47N3O. Calcuꢀ
lated (%): C, 74.02; H, 11.68; N, 10.36. IR, /cm–1: 3330 (NH),
1711 (C=O), 1656 (C=C). 1H NMR, : 1.06 (s, 27 H, 3 Me3CN);
1.26 (s, 1 H, NH); 1.61, 1.71 (both s, 3 H each, (CH3)2C=CH);
2.12 (d, 2 H, CH2CH=C, J = 7.5 Hz); 2.52 (s, 2 H, CCH2NH);
2.54, 3.02 (both d, 4 H each, 2 NCH2C, J = 11.0 Hz); 2.77 (d, 2 H,
NCH2C, J = 10.3 Hz); 2.99 (d, 2 H, NCH2C, J = 10.3 Hz);
5.17 (t, 1 H, CH=C, J = 6.0 Hz). 13C NMR, : 217.81
(CO(9)), 133.62 (C=), 120.22 (CH=), 56.32 (C(4), C(6)),
55.62 (C(2), C(8)), 53.50 (3,7ꢀCN), 50.49 (CNH), 50.19
(CH2NH), 49.99 (C(1)), 46.16 (C(5)), 32.09 (5ꢀCH2C=), 29.15
(NHC(CH3)3), 26.67 (2 C(CH3)3), 26.04, 17.95 (=C(CH3)2).
MS, m/z: found 406.3798 [M + H]+; C25H47N3O; calculated
M = 405.3719.
3,7ꢀDi(tertꢀbutyl)ꢀ1,5ꢀbis[(tertꢀbutyl)aminomethyl]ꢀ3,7ꢀdiꢀ
azabicyclo[3.3.1]nonanꢀ9ꢀone (5). A solution of acetone (2.90 g,
50 mmol), triazacyclohexane 1 (25.53 g, 100 mmol), and AcOH
(13.21 g, 120 mmol) in EtOH (100 mL) was refluxed for 6 h. The
reaction mixture was concentrated and alkalified with K2CO3 to
pH 10, and stirred. The product was extracted with boiling toluꢀ
ene (3×20 mL). The extract was concentrated and the residue
was recrystallized from EtOH. The yield of compound 5 was
8.50 g (40%), white crystals, m.p. 128—130 C (from EtOH).
Found (%): C, 71.16; H, 11.85; N, 12.98. C25H50N4O. Calcuꢀ
lated (%): C, 71.04; H, 11.92; N, 13.25. IR, /cm–1: 3323 (NH),
1706 (C=O). 1H NMR, : 0.97 (s, 18 H, 6 MeCN); 0.98 (s, 2 H,
2 NH); 0.99 (s, 18 H, 6 CH3CNH); 2.42 (s, 4 H, 2 CCH2NH);
2.90 (d, 4 H, 2 NCH2C, J = 10.3 Hz); 2.67 (d, 4 H, 2 NCH2C,
J = 10.3 Hz). 13C NMR, : 218.79 (CO(9)), 55.62 (C(2), C(4),
C(6), C(8)), 53.61 (3,7ꢀCN), 50.61 (2 CNH), 50.05 (2 CH2NH),
46.04 (C(1), C(5)), 29.21 (2 NHC(CH3)3), 26.78 (2 N—C(CH3)3).
MS, m/z: found 423.4048 [M + H]+; C25H50N4O; calculated
M = 422.3985.
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Received September 21, 2011;
in revised form December 7, 2011