1220
steroids 7 3 ( 2 0 0 8 ) 1217–1227
2.1.5. 3-Oxo-5˛-androst-17ˇ-yl-2ꢀ-methyl-1H-imidazole-
1-carboxylate (10)
was then concentrated under reduced pressure. Water (6 ml)
was added along with ethyl acetate (20 ml). The mixture was
left under magnetic stirring for a couple of hours and the
resulting aqueous phase was extracted with ethyl acetate (2×
30 ml) again. The organic phase was washed with aqueous
saturated NaHCO3 solution (10 ml) and water (10 ml), dried
over anhydrous Na2SO4, filtered, and the solvent was removed
under reduced pressure to afford compound 14 (83 mg; 82%),
which was recrystallized from a mixture of MeOH and water:
The method followed that described for compound 7 but using
17-hydroxy-5␣-androstan-3-one (4) (100 mg; 0.34 mmol) and
CBMI (104.7 mg; 0.55 mmol) in anhydrous acetonitrile (5 ml)
at reflux. After 29 h, more CBMI (26.6 mg; 0.14 mmol) was
added and 31 h later the reaction was complete. Compound
10 (96.6 mg; 94%): mp (acetonitrile) 195–196 ◦C; IR 1152, 1282,
1710, 1744 cm−1 1H NMR (CDCl3, 300 MHz) ı 0.92 (s, 3H, 18-H3),
;
mp 144–147 ◦C; IR 1716, 3423 cm−1 1H NMR (CDCl3, 300 MHz)
;
1.04 (s, 3H, 19-H3), 2.66 (s, 3H, 2ꢀ-CH3), 4.80 (m, 1H, 17␣-H), 6.88
(brs, 1H, 4ꢀ-H), 7.36 (brs, 1H, 5ꢀ-H); 13C NMR (CDCl3, 75 MHz) ı
11.4, 12.4, 16.8, 20.7, 23.4, 27.3, 28.6, 31.0, 35.0, 35.6, 36.7, 38.0,
38.4, 42.9, 44.5, 46.5, 50.2, 53.5, 86.8 (C17), 118.1 (C5ꢀ), 127.5 (C4ꢀ),
147.8 (C2ꢀ), 149.4 (OCO), 211.7 (C3). EI-MS m/z (%): 398 (24) M+,
273 (36), 255 (100), 159 (37), 123 (46), 107 (42), 81 (52), 79 (43);
Anal. calcd. for C24H34N2O3: C 72.33, H 8.60, N 7.03, found: C
72.16, H 8.74, N 7.31.
ı 0.76 (s, 3H, 18-H3), 1.04 (s, 3H, 19-H3), 2.04 (s, 3H, 3-OAc),
3.65 (m, 1H, 17␣-H), 4.60 (m, 1H, 3␣-H), 5.37 (m, 1H, 6-H); 13C
NMR (CDCl3, 75 MHz) ı 13.5, 19.4, 20.4, 21.3, 21.9, 27.6, 30.8,
31.3, 31.7, 35.8, 36.5, 36.8, 37.9, 47.4, 50.0, 51,6, 73.7 (C3); 81.4
(C17), 122.1 (C6), 139.5 (C5), 170.4 (CH3CO); EI-MS m/z (%): 332
(2) M+, 272 (100), 239 (56), 183 (26), 143 (45), 105 (44), 91 (54), 79
(40); Anal. calcd. for C21H32O3: C 75.86, H 9.70, found: C 75.50,
H 9.70.
2.1.6. 3-Oxoandrosta-1,4-dien-17ˇ-yl-2ꢀ-methyl-1H-
imidazole-1-carboxylate (11)
2.1.9. 3ˇ-Acetoxyandrost-5-en-17ˇ-yl-2ꢀ-methyl-1H-
imidazole-1-carboxylate (15)
The method followed that described for compound
7
but using 17-hydroxyandrosta-1,4-dien-3-one (5) (400 mg;
1.4 mmol) and CBMI (531.3 mg; 2.79 mmol) in anhydrous
dichloromethane (14 ml) at reflux for 28 h. Compound 11
(402.2 mg; 73%): mp (ethanol) 165–167 ◦C; IR 1149, 1280, 1625,
The method followed that described for compound 7 but
using compound 14 (596 mg; 1.79 mmol) and CBMI (657 mg;
3.45 mmol) in anhydrous acetonitrile (15 ml) at reflux for 29 h.
Compound 15 (611 mg; 77%): mp (ethyl acetate/n-hexane)
1664, 1761 cm−1 1H NMR (CDCl3, 300 MHz) ı 0.98 (s, 3H, 18-H3),
;
151–152 ◦C; IR 1147, 1302, 1725, 1750 cm−1 1H NMR (CDCl3,
;
1.26 (s, 3H, 19-H3), 2.66 (s, 3H, 2ꢀ-CH3), 4.79 (m, 1H, 17␣-H), 6.09
(brs, 1H, 4-H), 6.24 (m, 1H, 2-H), 6.88 (brs, 1H, 4ꢀ-H), 7.05 (m, 1H,
1-H), 7.35 (brs, 1H, 5ꢀ-H); 13C NMR (CDCl3, 75 MHz) ı 12.4, 16.8,
18.6, 22.2, 23.5, 27.2, 32.5, 32.9, 35.2, 36.4, 42.9, 43.3, 49.5, 51,9,
86.2 (C17), 118.0 (C5ꢀ), 124.0 (C4), 127.6 and 127.8 (C2 and C4ꢀ),
147.8 (C2ꢀ), 149.4 (OCO), 155.4 (C1), 168.5 (C5), 186.2 (C3). EI-MS
m/z (%): 394 (36) M+, 229 (10), 173 (37); 147 (80), 122 (73), 91 (76),
83 (100), 81 (22); Anal. calcd. for C24H30N2O3: C 73.07, H 7.66, N
7.10, found: C 73.26, H 7.60, N 7.25.
300 MHz) ı 0.92 (s, 3H, 18-H3), 1.05 (s, 3H, 19-H3), 2.04 (s, 3H,
3-OAc), 2.67 (s, 3H, 2ꢀ-CH3), 4.61 (m, 1H, 3␣-H), 4.80 (m, 1H,
17␣-H), 5.39 (m, 1H, 6-H), 6.87 (brs, 1H, 4ꢀ-H), 7.36 (brs, 1H, 5ꢀ-
H); 13C NMR (CDCl3, 75 MHz) ı 12.3, 16.8, 19.3, 20.3, 21.4, 23.4,
27.4, 27.6, 31.3, 31.6, 36.5, 36.6, 36.9, 38.0, 42.6, 49.7, 50.6, 73.7
(C3), 86.8 (C17), 118.1 (C5ꢀ), 122.0 (C6), 127.5 (C4ꢀ), 139.7 (C5),
147.8 (C2ꢀ), 149.4 (OCO), 170.5 (CH3CO). EI-MS m/z (%): 440 (8)
M+, 380 (100), 255 (78), 145 (65), 129 (89), 91 (56), 81 (72), 67 (46);
Anal. calcd. for C26
H36N2O4: C 70.88, H 8.24, N 6.36, found: C
2.1.7. 3-Oxo-5˛-androst-1-en-17ˇ-yl-2ꢀ-methyl-1H-
imidazole-1-carboxylate (12)
2.1.10. 5˛-Androstan-17ˇ-ol (17)
Details of the synthesis of this compound were reported pre-
viously [42].
The method followed that described for compound
7
but using 17-hydroxy-5␣-androst-1-en-3-one (6) (80 mg;
0.28 mmol) and CBMI (150.5 mg; 0.79 mmol) in anhydrous
dichloromethane (2.6 ml) at reflux for 5 h. Compound 12
(92.4 mg; 84%): mp (ethanol) 212–214 ◦C; IR 1152, 1283, 1674,
2.1.11. 5˛-Androstane-17ˇ-yl-2ꢀ-methyl-1H-imidazole-1-
carboxylate (18)
1745 cm−1 1H NMR (CDCl3, 600 MHz) ı 0.92 (s, 3H, 18-H3), 1.02
;
(s, 3H, 19-H3), 2.65 (s, 3H, 2ꢀ-CH3), 4.80 (m, 1H, 17␣-H), 5.85 (m,
1H, 2-H), 6.86 (brs, 1H, 4ꢀ-H), 7.11 (m, 1H, 1-H), 7.34 (brs, 1H,
5ꢀ-H); 13C NMR (CDCl3, 150.8 MHz) ı 12.6, 13.0, 16.7, 20.6, 23.3,
27.3, 27.4, 30.6, 35.3, 36.7, 38.9, 40.8, 43.0, 44.1, 49.7, 50.3, 86.8
(C17), 118.3 (C5ꢀ), 127.7 and 127.8 (C2 and C4ꢀ), 147.1 (C2ꢀ), 149.6
(OCO), 158.0 (C1), 200.1 (C3). EI-MS m/z (%): 396 (16) M+, 271 (14),
161 (26), 121 (31), 107 (100), 95 (54), 81 (31), 79 (26); Anal. calcd.
for C24H32N2O3: C 72.70, H 8.13, N 7.06, found: C 72.50, H 8.51,
N 7.20.
The method followed that described for compound 7 but
using compound 17 (379.2 mg; 1.37 mmol) and CBMI (521.1 mg;
2.74 mmol) in anhydrous dichloromethane (14 ml) at reflux.
After 27 h more CBMI (100.8 mg; 0.53 mmol) was added and 29 h
later the reaction was complete. The resulting white solid was
purified by flash chromatography (ethyl acetate:petroleum
ether 40–60 ◦C 2:1) to afford compound 18 (385.1 mg; 73%): mp
(acetone) 112–115 ◦C; IR 1149, 1273, 1751 cm−1; 1H NMR (CDCl3,
300 MHz) ı 0.80 (s, 3H, 18-H3), 0.89 (s, 3H, 19-H3), 2.66 (s, 3H, 2ꢀ-
CH3), 4.78 (m, 1H, 17␣-H), 6.87 (brs, 1H, 4ꢀ-H), 7.35 (brs, 1H, 5ꢀ-H);
13C NMR (CDCl3, 75 MHz) ı 12.1, 12.5, 16.8, 20.1, 22.0, 23.4, 26.7,
27.4, 28.7, 28.9, 31.5, 35.2, 36.2, 36.9, 38.6, 42.9, 46.9, 50.5, 54.5,
87.1 (C17), 118.1 (C5ꢀ), 127.3 (C4ꢀ), 147.8 (C2ꢀ), 149.4 (OCO). EI-MS
m/z (%): 384.1 (14) M+, 259 (73), 163 (69), 149 (100), 135 (52), 121
(47), 81 (71), 67 (56); Anal. calcd. for C24H36N2O2: C 74.96, H 9.44,
N 7.28, found: C 74.66, H 9.82, N 7.00.
2.1.8. 17ˇ-Hydroxyandrost-5-en-3ˇ-yl acetate (14)
DHEA acetate (13) (100 mg; 0.30 mmol) was dissolved in a mix-
ture of THF/MeOH 1:1 (2 ml) at room temperature. The mixture
was then cooled in an ice bath while NaBH4 (30 mg; 0.79 mmol)
was carefully added. After 1 h at room temperature, the reac-
tion was quenched by adding acetone dropwise. The mixture