Z. Iványi et al. / Steroids 77 (2012) 1152–1159
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6.36 (d, 1H, J = 1.5 Hz, 40-H), 7.60 and 7.69 (d, 2H, J = 7.5 Hz, 200- and
600-H, and d, 2H, J = 7.5 Hz, 300- and 500-H), 7.67 (d, 1H, J = 1.5 Hz, 30-
H). 13C NMR (d, ppm, CDCl3): 16.5 (C-18), 19.3 (C-19), 20.7, 30.5,
31.4, 31.5, 32.3, 34.7, 36.7, 37.1, 42.2, 48.4, 50.3, 56.9, 71.6 (C-3),
107.8 (C-40), 110.8 (C-400), 118.3 (CN), 121.1 (C-6), 125.7 and
132.8 (4C, C-200, C-300, C-500 and C-600), 133.5, 138.8, 141.0, 141.1,
143.1, 144.3.
56.6, 73.8 (C-3), 105.6 (C-40), 113.9 (2C, C-300, C-500), 122.5 (C-6),
127.3 (2C, C-200, C-600), 132.0, 134.0, 138.5, 139.2, 139.6, 142.9,
159.0, 160.6 (HCOO). Continued elution with diisopropyl ether/
hexane (1:1, v/v) resulted in pure 4e (with Method A: 170 mg,
6.4%; with Method B: 160 mg, 6.0%), mp 207–211 °C, Rf = 0.52 (ss
20
A);
C
[
a]
ꢀ 21 (c
1 in CHCl3). (Found C, 78.53; H, 8.32;
D
29H36N2O2 requires C, 78.34; H, 8.16%). 1H NMR (d, ppm, CDCl3):
1.08 (s, 6H, 18-H3, and 19-H3), 3.54 (m, 1H, 3-H), 3.83 (s, 3H, -
OCH3), 5.40 (s, 1H, 6-H), 6.16 (s, 1H, 16-H), 6.48 (d, 1H, J = 2.0 Hz,
40-H), 6.95 and 7.60 (d, 2H, J = 8.8 Hz, 200- and 600-H, and d, 2H,
J = 8.8 Hz 300- and 500-H), 7.74 (d, 1H, J = 2.0 Hz, 50-H). 13C NMR (d,
ppm, CDCl3): 16.2 (C-18), 19.3 (C-19), 21.0, 30.4, 31.6 (2C), 31.7,
35.5, 36.7, 37.2, 42.3, 46.9, 50.6, 55.5 (OCH3), 57.1, 71.8 (C-3),
105.3 (C-40), 114.4 (2C, C-300, C-500), 120.2 (2C, C-200, C-600), 121.5
(C-6), 126.7, 127.1, 134.2, 141.2, 147.5, 149.6, 157.8. Continued
elution with diisopropyl ether resulted in pure 5e (with Method
2.2.4. 17-(1-p-Tolyl-3-pyrazolyl)androsta-5,16-dien-3b-ol (4d), 17-
(1-p-tolyl-5-pyrazolyl)androsta-5,16-dien-3b-ol (5d) and 17-(1-p-
tolyl-5-pyrazolyl)androsta-5,16-dien-3b-yl formate (12d)
The resulting crude product was chromatographed on silica gel
with diisopropyl ether/hexane (1:4, v/v) to yield pure 12d (with
Method A: 140 mg, 5,1%), mp 153–158 °C, Rf = 0.62 (ss B);
20
[
a]
D
ꢀ 54 (c 1 in CHCl3). (Found C, 79.08; H, 7.61; C30H36N2O2 re-
quires C, 78.91; H, 7.95%). 1H NMR (d, ppm, CDCl3): 0.96 and 1.07
(s, 3H, 18-H3, and s, 3H, 19-H3), 2.39 (s, 3H, 400-CH3), 4.74 (m, 1H,
3-H), 5.35 (s, H, 16-H), 5.40 (d, 1H, J = 4.0 Hz, 6-H), 6.33 (d, 1H,
J = 1.8 Hz, 40-H), 7.18 and 7.26 (d, 2H, J = 8.0 Hz, 200- and 600-H,
and d, 2H, J = 8.0 Hz, 300- and 500-H), 7.61 (d, 1H, J = 1.8 Hz, 30-H),
8.03 (s, 1H, HCOO). 13C NMR (d, ppm, CDCl3): 16.4 (C-18), 19.2
(C-19), 20.8, 21.1, 27.7, 30.4, 31.4, 32.1, 34.9, 36.7, 36.8, 38.0,
48.0, 50.2, 56.6, 73.8 (C-3), 105.7 (C-40), 122.5 (C-6), 125.8 and
129.3 (4C, C-200, C-300, C-500 and C-600), 131.9, 137.5, 138.3, 138.5,
139.5, 139.7, 143.0, 160.6 (HCOO). Continued elution with diiso-
propyl ether/hexane (1:1, v/v) resulted in pure 4d (with Method
A: 980 mg, 37%; with Method B: 530 mg, 20%), mp 201–205 °C,
20
Rf = 0.38 (ss A); [
a
]
D
ꢀ 54 (c 1 in CHCl3). (Found C, 78.46; H,
8.37; C29H36N2O2 requires C, 78.34; H, 8.16%). 1H NMR (d, ppm,
CDCl3): 0.95 and 1.04 (s, 3H, 18-H3, and s, 3H, 19-H3), 3.50 (m,
1H, 3-H), 3.84 (s, 3H, -OCH3), 5.34 (s, 2H, 6-H and 16-H), 6.32 (s,
1H, 40-H), 6.91 and 7.28 (d, 2H, J = 7.8 Hz, 200- and 600-H and d, 2H,
J = 7.8 Hz 300- and 500-H), 7.60 (s, 1H, 30-H). 13C NMR (d, ppm, CDCl3):
16.4 (C-18), 19.3 (C-19), 20.8, 30.4, 31.4, 31.6, 32.1, 35.0, 36.7, 37.1,
42.2, 48.1, 50.3, 55.5 (OCH3) 56.6, 71.6 (C-3), 105.6 (C-40), 113.9
(2C, C-300, C-500), 121.2 (C-6), 127.3 (2C, C-200, C-600), 132.0, 134.0,
138.6, 139.2, 141.1, 142.9, 159.0.
A: 170 mg, 6.6%; with Method B: 190 mg, 7.4%), mp 196–199 °C,
20
Rf = 0.46 (ss A); [
a]
ꢀ 28 (c 1 in CHCl3). (Found C, 81.05; H,
D
8.65; C29H36N2O requires C, 81.27; H, 8.47%). 1H NMR (d, ppm,
CDCl3): 1.08 and 1.09 (s, 3H, 18-H3, and s, 3H, 19-H3), 2.37 (s,
3H, 400-CH3), 3.54 (m, 1H, 3-H), 5.39 (d, 1H, J = 5.0 Hz, 6-H), 6.17
(s, 1H, 16-H), 6.49 (s, 1H, J = 2.3 Hz, 40-H), 7.22 and 7.57 (d, 2H,
J = 8.3 Hz, 200- and 600-H, and d, 2H, J = 8.3 Hz, 300- and 500-H), 7.80
(s, 1H, J = 2.3 Hz, 50-H). 13C NMR (d, ppm, CDCl3): 16.2 (C-18),
19.3 (C-19), 20.9, 21.0 (400-CH3), 30.4, 31.6 (2C), 31.8, 35.5, 36.7,
37.2, 42.3, 46.9, 50.6, 57.1, 71.8 (C-3), 105.5 (C-40) 118.6 and
129.8 (4C, C-200, C-300, C-500 and C-600), 121.5 (C-6), 126.6, 127.3,
135.5, 138.1, 141.2, 147.5, 149.6. Continued elution with diisopro-
pyl ether resulted in pure 5d (with Method A: 810 mg, 32%; with
2.3. General procedure for the preparation of 17-(3(5)-
pyrazolyl)androsta-5,16-dien-3b-ol (7) and 17b-[3(5)-
pyrazolyl]androst-5-en-3b-ol (10)
Compound 2 [7] or 9 [23] (6 mmol) was dissolved in glacial ace-
tic acid (75 ml) and hydrazine hydrate (6 ml) was added. The reac-
tion mixture was stirred at room temperature for 6 h, and was then
poured into ice-cold water (500 ml). The precipitate that formed
was filtered off and washed with water. The residue obtained
was dissolved in ethyl acetate/CH2Cl2 and chromatographed on sil-
ica gel to afford 7 and 10.
Method B: 550 g, 21%), mp 138–144 °C, Rf = 0.44 (ss A);
20
[
a]
D
ꢀ 43 (c 1 in CHCl3). (Found C, 81.12; H, 8.55; C29H36N2O re-
2.3.1. 17-[3(5)-Pyrazolyl]androsta-5,16-dien-3b-ol (7)
quires C, 81.27; H, 8.47%). 1H NMR (d, ppm, CDCl3): 0.96 and 1.04
(s, 3H, 18-H3, and s, 3H, 19-H3), 2.39 (s, 3H, 400-CH3), 3.50 (m, 1H,
3-H), 5.35 (overlapping multiplets, 2H, 6-H and 16-H), 6.35 (s,
1H, 40-H), 7.20 and 7.26 (d, 2H, J = 8.0 Hz, 200- and 600-H, and d,
2H, J = 8.0 Hz, 300- and 500-H), 7.66 (s, 1H, 30-H). 13C NMR (d, ppm,
CDCl3): 16.4 (C-18), 19.3 (C-19), 20.8, 21.1, 30.4, 31.4, 31.5, 32.1,
35.0, 36.7, 37.1, 42.2, 48.1, 50.3, 56.7, 71.6 (C-3), 105.8 (C-40),
121.1 (C-6), 125.8 and 129.4 (4C, C-200, C-300, C-500 and C-600),
132.7, 137.8, 138.0, 138.8, 138.9, 141.1, 142.6.
The resulting crude product 7 was chromatographed on silica gel,
starting with ethyl acetate/CH2Cl2 (10:90, v/v) as eluent, followed by
ethyl acetate/CH2Cl2 (40:60, v/v), to afford pure 7 (1.69 g, 83%). mp
219–221 °C (Ref. [7]: mp 216–220 °C, Ref. [23]: mp 222–223.5 °C),
20
Rf = 0.18 (ss A); [
C
a]
ꢀ 40 (c 1 in CDCl3). (Found C, 77.97; H, 9.11;
D
22H30N2O requires C, 78.06; H, 8.93%). 1H NMR (d, ppm, DMSO-
d6): 0.93 (s, 3H, 18-H3), 0.99 (s, 3H, 19-H3), 3.26 (m, 1H, 3-H), 4.62
(d, 1H, J = 4.0 Hz, 3-OH) 5.29 (d, 1H, J = 2.5 Hz, 6-H), 6.05 (s, 1H, 40-
H), 6.29 (s, 1H, 16-H), 7.52 (d, 1H, 50 (30)-H), 13.4 (s, 1H, NH). 13C
NMR (d, ppm, DMSO-d6): 16.0 (C-18), 19.0 (C-19), 20.5, 29.9, 31.0,
31.1, 34.8, 36.2, 36.8, 42.2, 46.2, 50.0, 56.5, 70.0 (C-3), 102.1 (C-40),
120.2 (C-6), 141.5 (C-5).
2.2.5. 17-(1-p-Methoxyphenyl-3-pyrazolyl)androsta-5,16-dien-3b-ol
(4e), 17-(1-p-methoxyphenyl-5-pyrazolyl)androsta-5,16-dien-3b-ol
(5e), and 17-(1-p-methoxyphenyl-5-pyrazolyl)androsta-5,16-dien-
3b-yl formate (12e)
2.3.2. 17b-[3(5)-Pyrazolyl]androst-5-en-3b-ol (10)
The resulting crude product was chromatographed on silica gel
with diisopropyl ether/hexane (1:4, v/v) to yield pure 12e (with
The resulting crude product 10 was chromatographed on silica
gel with ethyl acetate/CH2Cl2 (40:60, v/v) to afford pure 10 (1.36 g,
Method A: 240 mg, 8.5%), mp 164–167 °C, Rf = 0.42 (ss B);
67%). mp 218–222 °C (Ref. [23]: mp 233–235.5 °C, Ref. [7]: mp
20
20
D
[
a]
D
ꢀ 57 (c 1 in CHCl3). (Found C, 76.35; H, 7.92; C30H36N2O3 re-
222–227 °C), Rf = 0.14 (ss A); [
a]
ꢀ 64 (c 1 in CHCl3). (Found C,
quires C, 76.24; H, 7.68%). 1H NMR (d, ppm, CDCl3): 0.96 and 1.06
(s, 3H, 18-H3, and s, 3H, 19-H3), 3.84 (s, 3H, -OCH3), 4.73 (m, 1H,
3-H), 5.34 (s, 1H, 16-H), 5.40 (d, 1H, J = 3.5 Hz, 6-H), 6.32 (s, 1H,
40-H), 6.91 and 7.28 (d, 2H, J = 7.8 Hz, 200- and 600-H, and d, 2H,
J = 7.8 Hz, 300- and 500-H), 7.60 (s, 1H, 30-H), 8.03 (s, 1H, HCOO).
13C NMR (d, ppm, CDCl3): 16.4 (C-18), 19.2 (C-19), 20.8, 27.7,
30.4, 31.4, 32.1, 35.0, 36.7, 36.8, 38.0, 48.0, 50.2, 55.5 (OCH3),
77.52; H, 9.62; C22H32N2O requires C, 77.60; H, 9.47%). 1H NMR
(d, ppm, DMSO-d6): 0.44 (s, 3H, 18-H3), 0.93 (s, 3H, 19-H3), 2.64
(t, 1H, J = 9.5 Hz), 3.26 (m, 1H, 3-H), 4.62 (d, 1H, J = 4.0 Hz, OH)
5.28 (s, 1H, 6-H), 6.01 (s, 1H, 40-H), 7.43 (s, 1H, 50 (30)-H), 12.4 (s,
1H, NH). 13C NMR (d, ppm, DMSO-d6): 12.8 (C-18), 19.1 (C-19),
20.3, 24.1, 26.1, 31.3, 31.4, 31.8, 36.1, 36.9, 37.2, 42.2, 43.0, 49.8,
55.4, 69.9 (C-3), 102.9 (C-40), 120.3 (C-6), 141.2 (C-5).