1
600
K. LAO ET AL.
2
.1.11. General procedure for the preparation of 2-methylene-17- 2.1.16. General procedure for the preparation of 2-methylene-17b-
formamido-androst-4-ene-3-one (8a–8e)
To the solution of 1 mmol corresponding 2-hydroxymethylene Yield: 73% of pure product, m.p. 135–142 C. H NMR (CDCl3,
product in 8 ml acetone, 0.33 ml formaldehyde was added. The 300 Hz) d: 0.53 (m, 4H, –CH –CH –), 0.69 (s, 3H, 18-CH ), 1.06 (s,
(N-cyclopropylamino-carbonyl)-androst-4-ene-3-one (8e)
ꢂ
1
2
2
3
resulting mixture was stirred at room temperature for 2 h. Upon 3H, 19-CH ), 2.75 (m, 4H, –NH–CH–), 5.45 (s, 1H, 4-H), 6.23 (s, 2H,
3
completion, the reaction mixture was poured into 30 ml water and 2-ethylene) ppm. 13C NMR (101 MHz, CDCl ) d: 13.18, 18.56, 20.20,
3
extracted with ethyl acetate. The combined organic layers were
dried and the solvent was evaporated in vacuo to provide yellow
solid. The compound was purified by column chromatography
2
4
1
1.20, 23.68, 24.42, 28.61, 29.69, 31.75, 32.65, 35.63, 38.39, 40.77,
3.64, 45.07, 46.86, 53.11, 55.59, 57.19, 76.70, 77.01, 77.33, 120.25,
24.54, 141.28, 171.70, 172.39, 188.77 ppm. HRMS (ESI): m/z
(PE/ethyl acetate, 2:1).
þ
[M þ H] . Calcd for C H NO : 367.2520; Found: 367.2511.
2
4
33
2
2
.1.12. General procedure for the preparation of 2-methylene-17b-
2
.1.17. General procedure for the preparation of General proced-
(
N-isobutyl-carboxamide)-androst-4-ene-3-one (8a)
ꢂ
1
Yield: 55% of pure product, m.p. 168–175 C. H NMR (CDCl
00 Hz) d: 0.75 (s, 3H, 18-CH ), 1.07 (s, 3H, 19-CH ), 1.47 (d, 6H, one (9a–9e)
CH-(CH ), 3.52 (m, 2H, –NH–CH –), 5.20 (s, 1H, 2-ethylene), 5.81 To the solution of 1 mmol, corresponding 2-hydroxymethylene
s, 1H, 4-H), 5.91 (s, 1H, 2-ethylene) ppm. 13C NMR (75 MHz, product in 8 ml hydrazine hydrate. The resulting mixture was
3
,
ure for the preparation of 4-oxa-17-formamido-5a-androst-3-
3
3
3
)
3 2
2
(
CDCl ) d: 13.00, 13.40, 14.22, 18.04, 20.69, 24.19, 25.30, 31.34,
3
refluxed for 2 h. Upon completion, the reaction mixture was
poured into 30 ml water. The resulting precipitate was filtered,
washed with water, and dried to give white solid. The compound
was purified by column chromatography (PE/Ethyl acetate, 1:1).
3
5
1
3
2.20, 35.12, 38.22, 39.75, 40.28, 41.39, 44.39, 44.52, 50.41, 52.61,
5.32, 76.17, 76.59, 77.02, 119.75, 123.95, 140.79, 171.45, 171.65,
þ
88.33 ppm. HRMS (ESI): m/z [M þ H] . Calcd for C25
2
H37NO :
83.2824; Found: 383.2897.
2
.1.13. General procedure for the preparation of 2-methylene-17b- 2.1.18. General procedure for the preparation of 17b-(N-isobutyl-
carboxamide)-androst[3,2-c]pyrazole-4-ene (9a)
(piperidine-1-carbonyl)-androst-4-ene-3-one (8 b)
ꢂ
1
ꢂ
1
Yield: 42% of pure product, m.p. 150–155 C. H NMR (CDCl
3
,
Yield: 20.01% of pure product, m.p.:189–195 C. H NMR(CDCl
3
,
3
4
1
1
4
1
00 Hz) d: 0.67 (s, 3H, 18-CH
3
), 1.00 (s, 3H, 19-CH
3
), 2.9 6–3.55 (m, 300 MHz) d: 0.51 (m, 2H, ꢀCHCH CH ꢀ), 0.75 (s, 3H, 18-CH ), 0.87
2
2
3
H, –NH–(CH
2 2
) –), 5.09 (s, 1H, 2-ethylene), 5.71 (s, 1H, 4-H), 5.81 (s, (m, 2H, ꢀCHCH CH ꢀ), 1.11 (s, 3H, 19-CH ), 2.76 (s, 1H, ꢀN(CH)),
2
2
3
H, 2-ethylene) ppm. 13C NMR (75 MHz, CDCl ) d: 13.49, 13.9, 5.47 (s, 1H, ꢀCONHꢀ), 5.82 (s, 1H, 4-H), 7.41 (s, 1H, 5-pyrazole)
3
4.71, 18.54, 21.22, 24.7, 25.84, 31.88, 32.7, 35.66, 38.77, 40.27, ppm. 13C NMR (75 MHz, CDCl ) d: 13.02, 13.46, 14.21, 17.94, 21.11,
3
0.79, 41.91, 44.9, 45.06, 50.97, 53.17, 55.88, 76.61, 77.03, 77.46, 24.38, 25.35, 31.14, 31.79, 33.6, 36.04, 38.63, 39.77, 41.42, 44.59,
20.21, 124.48, 141.31, 171.86, 172.18, 188.81 ppm. HRMS (ESI): m/ 50.6, 53.65, 55.55, 76.15, 76.57, 77, 111.71, 111.84, 127.16, 148.76,
þ
þ
z [M þ H] . Calcd for C26
2
H37NO : 395.2832; Found: 395.2824.
1
3
71.95 ppm. HRMS (ESI): m/z [M þ H] . Calcd for C24
33 3
H N O:
80.2628; Found: 380.2951.
2
3
.1.14. 2-methylene-17b-(N,N-diethy-carboxamide)-androst-4-ene-
-one (8c)
ꢂ
1
2.1.19. General procedure for the preparation of 17b-(Piperidine-
3 3
), 1.12 (s, 3H, 19-CH
), 2.8 7–3.09 (m, 1-carbonyl)- androst[3,2-c]pyrazole -4-ene (9 b)
Yield: 68% of pure product, m.p. 98–105 C. H NMR (CDCl3,
3
4
5
00 Hz) d: 0.61 (s, 3H, 18-CH
H, –NH– (CH
–), 5.09 (s, 1H, –CONH–), 5.30 (s, 1H, 2-ethylene), Yield: 45.20% of pure product, m.p.:154–162 C; H NMR(CDCl
.70 (s, 1H, 4-H),5.80 (s, 1H, 2-ethylene) ppm. C NMR (75 MHz, 300 MHz) d: 0.77 (s, 3H, 18-CH
), 6.18 (s, 1H, 4-H), 6.54 (s, 1H, –CONH–), 7.22 (s, 1H, 5-pyra-
5.66, 38.77, 40.27, 40.79, 41.91, 44.9, 45.06, 50.97, 53.17, 55.88, zole) ppm. 13C NMR (75 MHz, CDCl ) d: 13.01, 13.42, 14.2, 17.95,
ꢂ
1
)
2 2
3
,
13
3
3
), 0.95 (s, 3H, 19-CH ), 3.56 (m, 4H,-
2 2
CDCl ) d: 13.49, 13.90, 14.71, 18.54, 21.22, 24.70, 25.84, 31.88, 32.7, N(CH )
3
3
7
1
2
3
6.61, 77.03, 77.46, 120.21, 124.48, 141.31, 171.86, 172.18, 22.12, 24.39, 25.36, 31.15, 31.79, 33.58, 36.06, 38.62, 38.65, 39.73,
88.81 ppm. HRMS (ESI): m/z [M þ H] . Calcd for C25
þ
H
37NO
2
:
41.37, 44.55, 50.64, 53.67, 55.60, 92.74, 111.72, 112.07, 166.15 ppm.
þ
83.2826; Found: 283.2824.
HRMS (ESI): m/z [M þ H] . Calcd for C H N O : 408.2940;
2
6 37 3 2
Found: 408.3009.
2
.1.15. General procedure for the preparation of 2-methylene-17b-
(
N-(3,4-dimethoxyphenethyl)-carboxamide)-androst-4-ene-3-
2
.1.20. General procedure for the preparation of 17b-(N,N-diethy-
one (8d)
ꢂ
1
carboxamide)-androst[3,2-c]pyrazole-4-ene (9c)
Yield: 47.91% of pure product, m.p.:111–118 C; H NMR(CDCl3,
Yield: 65% of pure product, m.p. 74–78 C. H NMR (CDCl , 300 Hz)
d: 0.74 (s, 3H, 18-CH ), 1.01 (s, 3H, 19-CH ), 3.53 (m, 4H, N-CH -
3
ꢂ
1
3
3
2
3
–
00 MHz) d: 0.77 (s, 3H, 18-CH
NCH ), 6.18 (s, 1H, 4-H), 0.95 (s, 3H, 19-CH
) d: 13.07, 18.03, 21.25, 23.57,
3 2
), 3.01 (m, 4H, –NCH ), 3.76 (m, 4H,
CH
OCH
ppm. 13C NMR (75 MHz, CDCl
2
-Ar), 5.29 (s, 1H, 2-ethylene), 5.35 (s, 1H, –CONH–), 3.92 (s, 6H,
), 5.89 (s, 1H, 4-H), 6.00 (s, 1H, 2-ethylene), 6.85 (m, 3H, Ar-H)
) d: 12.59, 17.54, 20.72, 23.04, 23.93,
2
3
), 7.21 (s, 1H, 5-pyra-
-
3
zole) ppm. 13C NMR (101 MHz, CDCl
3
3
3
5
1
1
4
0.81, 31.88, 34.94, 35.18, 37.03, 37.63, 39.36, 40.09, 43.07, 52.55, 24.44, 31.33, 32.38, 35.44, 35.73, 37.57, 38.2, 39.88, 40.56, 43.57,
4.95, 55.34, 55.43, 56.47, 76.18, 76.6, 77.03, 110.77, 111.33, 53.1, 55.5, 55.87, 55.97, 57.03, 76.71, 77.03, 77.34, 106.37, 111.41,
20.14, 122.49, 130.91, 147.14, 148.52, 164.75, 169.43, 172.02, 111.94, 120.66, 123, 131.44, 147.75, 149.13, 165.39, 169.76, 172.47,
þ
þ
88.58 ppm. HRMS (ESI): m/z [M þ H] . Calcd for C31
H
41NO
4
:
188.95 ppm. HRMS (ESI): m/z [M þ H] . Calcd for C29
H N O:
37 3
91.3036; Found: 491.3107.
396.2941; Found: 396.3013.