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D. V. N. S. Rao, G. N. Trinadhachari, K. J. Prabahar, R. Dandala, M. Sivakumaran and A. Naidu
Vol 44
Table 2
1H-NMR Spectral Data of Compounds 4a-f, 5a-f and 6
1H-NMR (ꢂ, ppm, in deuteriochloroform)
Compd.
4a
4b
4c
4d
4e
4f
0.72 (s, 3H, CH3), 0.93-1.11 (m, 3H), 1.22 (s, 3H, CH3), 1.30-1.34 (m, 3H), 1.36 (s, 9H, tBu), 1.41 (m, 3H), 1.67-1.75 (m,
3H), 1.78-1.83 (m, 2H), 1.96-2.06 (m, 3H), 2.15-2.18 (m, 1H), 2.48-2.68 (m, 2H), 3.68 (dd, 1H, J = 3.2, 11.8 Hz, C5-H),
5.10 (s, 1H, N-H), 7.26-7.90 (m, 5H, Ar-H)
0.71 (s, 3H, CH3), 1.01 (m, 3H, CH3), 1.26-1.32 (m, 3H), 1.35 (s, 9H, Bu), 1.48-1.57 (m, 3H), 1.61-1.72 (m, 3H), 1.77-
1.80 (m, 3H), 1.83-1.88 (m, 2H), 1.90-2.07 (m, 3H), 2.12-2.18 (m, 1H), 2.53-2.57 (m, 2H), 3.84 (dd, 1H, J = 2.4, 11.8 Hz,
C5-H), 5.10 (s, 1H, N-H), 7.26-8.13 (m, 4H, Ar-H)
0.71 (s, 3H, CH3), 0.93-1.1 (m, 3H), 1.24 (m, 3H, CH3), 1.23-1.90 (m, 3H), 1.35 (s, 9H, tBu), 1.39-1.56 (m, 3H), 1.65-1.75
(m, 4H), 1.85-1.91 (m, 1H), 1.96-2.06 (m, 3H), 2.14-2.17 (m, 1H), 2.50-2.56 (m, 1H), 2.63-2.70 (m, 1H), 3.69 (dd, 1H, J =
3.2, 11.8 Hz, C5-H, N-H), 5.09 (s, 1H, N-H), 7.64 (t, 1H, J = 7.9, Ar-H), 8.11-8.61 (m, 3H, Ar-H)
0.72 (s, 3H, CH3), 0.93-0.98 (m, 1H), 1.02-1.14 (m, 2H), 1.21 (s, 3H, CH3), 1.25-1.29 (m, 2H), 1.35 (s, 9H, tBu), 1.42-1.51
(m, 3H), 1.57 (s, 3H), 1.66-1.75 (m, 3H), 1.90-2.03 (m, 3H), 2.14-2.17 (m, 1H), 2.43-2.49 (m, 1H), 2.61-2.67 (m, 1H),
3.68 (dd, 1H, J = 3.2, 11.8 Hz, C5-H), 5.09 (s, 1H, N-H), 7.92 (d, 2H, J = 9.0 Hz, Ar-H), 8.27 (d, 2H, J = 9.0 Hz, Ar-H)
0.71 (s, 3H, CH3), 0.92-1.11 (m, 3H), 1.20 (s, 3H, CH3), 1.23-1.30 (m, 3H), 1.36 (s, 9H, tBu), 1.42-1.56 (m, 3H), 1.66-1.72
(m, 3H), 1.75-1.77 (m, 2H), 1.95-2.06 (m, 3H), 2.11-2.18 (m, 1H), 2.50-2.56 (m, 1H), 2.59-2.65 (m, 1H), 3.64 (dd, 1H, J =
3.2, 11.8 Hz, C5-H), 3.87 (s, 3H, OCH3), 5.10 (s, 1H, N-H), 6.95 (d, 2H, J = 9.1 Hz, Ar-H), 7.90 (d, 2H, J = 9.1 Hz, Ar-H)
0.70 (s, 3H, CH3), 0.91-1.11 (m, 3H), 1.21 (s, 3H, CH3), 1.26-1.31 (m, 3H), 1.35 (s, 9H, tBu), 1.41-1.55 (m, 3H), 1.66-1.76
(m, 4H), 1.79-1.80 (m, 1H), 1.95-2.05 (m, 3H), 2.13-2.17 (m, 1H), 2.39 (s, 3H, CH3), 2.52-2.54 (m, 1H), 2.59-2.66 (m,
1H), 3.64 (dd, 1H, J = 3.2, 11.8 Hz, C5-H), 5.08 (s, 1H, N-H), 7.26-7.38 (m, 2H, Ar-H), 7.65 (d, 1H, J = 7.4 Hz, Ar-H),
7.70 (s, 1H, Ar-H)
t
5a
5b
5c
5d
5e
5f
0.73 (s, 3H, CH3), 1.08-1.17 (m, 3H), 1.27 (s, 3H, CH3), 1.25-1.31 (m, 2H), 1.37 (s, 9H, tBu), 1.44-1.56 (m, 3H), 1.67-1.87
(m, 2H), 2.01-2.08 (m, 2H), 2.15-2.23 (m, 2H), 3.85 (dd, 1H, J = 3.2, 12.1 Hz, C5-H), 5.12 (s, 1H, N-H), 5.88 (d, 1H, J =
10.1 Hz, C2-H), 7.03 (d, 1H, J = 10.1 Hz, C5-H), 7.28-7.93 (m, 5H, Ar-H)
0.74 (s, 3H, CH3), 0.97-1.17 (m, 3H), 1.21 (s, 3H, CH3), 1.25-1.33 (m, 2H), 1.35 (s, 9H, tBu), 1.46-1.56 (m, 2H), 1.67-1.79
(m, 3H), 1.80-1.93 (m, 1H), 2.01-2.07 (m, 2H), 2.12-2.18 (m, 1H), 2.46-2.54 (m, 2H), 3.79 (dd, 1H, J = 2.4, 11.8 Hz, C5-
H), 5.09 (s, 1H, N-H), 5.74 (d, 1H, J = 10.1 Hz, C2-H), 7.01 (d, 1H, J = 10.1 Hz, C5-H), 7.34 –8.28(m, 4H, Ar-H)
0.73 (s, 3H, CH3), 1.05-1.23 (m, 3H), 1.29 (s, 3H, CH3), 1.25-1.31 (m, 2H), 1.36 (s, 9H, tBu), 1.42-1.57 (m, 3H), 1.67-1.87
(m, 4H), 2.02-2.08 (m, 2H), 2.11-2.18 (m, 1H), 2.29-2.35 (m, 1H), 3.8 6 (dd, 1H, J = 2.4, 11.8 Hz, C5-H), 5.09 (s, 1H, N-
H), 5.86 (d, 1H, J = 10.1 Hz, C2-H), 7.10 (d, 1H, J = 10.1 Hz, C5-H), 7.64 (t, 1H, J = 7.9 Hz), 8.13-8.61 (m, 3H, Ar-H)
0.73 (s, 3H, CH3), 1.06-1.23 (m, 3H), 1.27 (s, 3H, CH3), 1.25-1.31 (m, 2H), 1.36 (s, 9H, tBu), 1.44-1.52 (m, 3H), 1.64-1.86
(m, 4H), 2.02-2.07 (m, 2H), 2.11-2.21 (m, 1H), 2.35-2.41 (m, 1H), 3.85 (dd, 1H, J = 2.4, 11.8 Hz, C5-H), 5.09 (s, 1H, N-
H), 5.85 (d, 1H, J = 10.1 Hz, C2-H), 7.10 (d, 1H, J = 10.1 Hz, C5-H), 7.95 (d, 2H, J = 8.8 Hz), 8.27 (d, 2H, J=8.8 Hz)
0.71 (s, 3H, CH3), 1.04-1.18 (m, 3H), 1.23 (s, 3H, CH3), 1.22-1.32 (m, 2H), 1.35 (s, 9H, tBu), 1.41-1.58 (m, 3H), 1.63-1.74
(m, 2H), 1.80-1.85 (m, 2H), 2.01-2.20 (m, 4H), 3.78 (dd, 1H, J = 2.4, 11.8 Hz, C5-H), 3.86 (s, 3H, OCH3), 5.09 (s, 1H, N-
H), 5.89 (d, 1H, J = 10.1 Hz), 6.94 (d, 2H J = 9.1 Hz), 6.98 (d, 1H, J = 10.1 Hz, C5-H), 7.90 (d, 2H, J = 9.1 Hz).
0.71(s, 3H, CH3), 1.06-1.15 (m, 2H), 1.26 (s, 3H, CH3), 1.22-1.29 (m, 2H), 1.36 (s, 9H, tBu ), 1.39-1.53 (m, 3H), 1.65-1.77
(m, 3H), 1.80-1.86 (m, 1H), 2.01-2.08 (m, 2H), 2.10-2.17 (m, 2H), 2.39 (s, 3H, CH3), 3.82 (dd, 1H, J = 2.4, 11.8 Hz, C5-
H), 5.10 (s, 1H, N-H), 5.87 (d, 1H, J = 10.1 Hz, C2-H), 7.01 (d, 1H, J = 10.1 Hz, C5-H), 7.30-7.38 (m, 2H, J = 9.1 Hz)
7.68-7.70 (m, 1H,Ar-H), 7.72 (s, 1H, Ar-H).
6
0.71 (s, 3H, CH3), 0.97 (s, 3H, CH3), 1.06-1.15 (m, 3H), 1.22-1.29 (m, 2H), 1.36 (s, 9H, tBu), 1.40-1.48 (m, 2H), 1.57-1.65
(m, 3H), 1.67-1.77 (m, 3H), 1.95-2.06 (m, 2H), 2.15-2.22 (m, 1H), 3.32 (dd, 1H, J = 2.4, 11.7 Hz), 5.11 (s, 1H, N-H), 5.79
(d, 1H, J = 10.1 Hz, C2-H), 6.06 (s, 1H, N-H), 6.78 (d, 1H, J = 10.1 Hz, C5-H).
17ꢀ-(N-tert-Butyl carbamoyl)-4-aza-5ꢁ-androst-1-ene-3-
one (6). To a suspension of 5a (80 g, 0.168 moles) in ethanol (480
ml) was added a 70% aqueous ethylamine solution (54.02 g, 0.840
moles) and the resulting solution was stirred at 25-30 °C for 12
hours. Then, the reaction mass was concentrated under reduced
pressure, and was added tetrahydrofuran (160 ml), ethyl acetate
(160 ml) and water (480 ml). The resulting precipitate was stirred
at 3-5 °C for 2 hours. The product was filtered, washed with
water. This crude product was crystallized from a mixture of
tetrahydrofuran (400 ml) and ethyl acetate (400 ml) to obtain 55.2
g (88%) of 6 as a white crystalline product with a purity of 99.9%
as seen by HPLC method. (Having 0.05% of impurity 1, 0.01% of
impurity 3). Physical and spectral data of 6 are given in Tables 1
and 2. Similarly the compounds 5b-f can be treated with 70%
aqueous ethylamine solution to get 6 by this procedure. Physical
and spectral data of 6 are given in Tables 1 and 2.
Acknowledgement. Authors thank the management of
Aurobindo pharma Ltd., Hyderabad for the permission to
publish this work. Authors also thank the entire analytical
research department for the valuable contribution to this
work.
REFERENCES AND NOTES
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J. R.; Berman, C. J. Med. Chem. 1986, 29, 2298.
[2] Smith L. S.; Tegeler, J. J. Advances in dermatology, Ann.
Rep. Med. Chem. 1989, 24, 1177.
[3] Brooks, J. R. Clin. Endocrinol. Metab. 1986, 15, 391.
[4] Rasmusson G. H.; Reynolds, G. F. European Patent 155, 096,
1985; Chem. Abstr. 1986, 105, 60814q.