B. Yu et al. / Steroids 78 (2013) 494–499
497
3
CDCl
H, –OCOCH
3
), 1.05 (s, 6H, 18-H and H-19). 13C NMR (100 MHz,
Table 2
Optimization of reaction conditions for formation of compound 4c.a
3
): d 174.96, 170.58, 164.98, 140.07, 138.03, 134.69, 134.21,
1
3
1
5
30.99, 128.89, 121.56, 116.31, 98.83, 73.69, 52.44, 49.46, 47.14,
Entry
Base
Solvent
Yieldb (%)
8.02, 36.68, 34.70, 31.58–31.07, 27.64, 21.42, 21.07, 19.29,
1
2
3
4
5
6
7
8
9
Imidazole
DMAP
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
DCM
EtOAc
MeCN
Acetone
Toluene
15
0
0
+
6.51, 15.27. HRMS (ESI): m/z calcd. for C31
H
36ClN
2
O
3
(M + H) ,
19.2414; found, 519.2411.
Basic Al
Et
2
O
3
3
N
20
86
65
0
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
2
.4.4. 3b-Acetoxyl-5-en-16-(3-chlorobenzylidene) – androstano-17-
2-amino-1-cyano-2-oxoethy-lidene) (4d)
Yellow solid, yield 84%, mp 147.0–148.2 °C. H NMR (400 MHz,
CDCl ): d 7.38 (s, 1H, ArH), 7.36–7.24 (m, 3H, ArH), 7.18 (s, 1H, Ar–
CH=), 6.04 (m, 2H, –NH ), 5.40 (d, J = 4.7 Hz, 1H, 6-H), 4.71–4.49 (m,
H, 3 -H), 2.04 (s, 3H, –OCOCH
NMR (100 MHz, CDCl ): d 174.60, 170.51, 164.71, 140.02, 138.89,
37.91, 134.55, 133.83, 129.80, 129.43, 128.65, 127.81, 121.52,
c
(
1
0
Trace
0
0
3
1
1
0
1
2
1
3
1
a
3
), 1.05 (s, 6H, 18-H and H-19).
C
a
Unless otherwise noted, the reaction was carried out with 3 (0.1 mmol) and 4-
chlorobenzaldehyde (0.1 mmol) and Bases (0.2 mmol) under reflux in solvent (3 ml)
for about 3 h.
3
1
1
3
b
16.16, 99.18, 73.64, 54.81, 52.39, 49.42, 47.13, 37.99, 36.65,
4.67, 31.51, 31.05, 29.66, 27.60, 21.37, 21.03, 19.25, 16.48. HRMS
Isolated yields.
c
Under the same conditions except that the amount of catalyst was increased to
+
0.6 mmol.
(
ESI): m/z calcd. for C31
H35ClN
2
NaO
3
(M + Na) , 541.2234; found,
5
41.2230.
2
(
.4.7. 3b-Acetoxyl-5-en-16-(2- cyanobenzylidene) – androstano-17-
2-amino-1-cyano-2-oxoethy-lidene) (4g)
Brown solid, yield 55%, mp 211.7–212.5 °C. H NMR (400 MHz,
CDCl ): d 7.77–7.52 (m, 4H, ArH), 7.47–7.36 (m, 1H, Ar–CH=), 6.27
s, 1H, –NH ), 6.06 (s, 1H, –NH ), 5.38 (d, J = 5.1 Hz, 1H, 6-H), 4.73–
.50 (m, 1H, 3 -H), 2.05 (s, 3H, –OCOCH ), 1.12 (s, 3H, 18-H), 1.07
): d 172.42, 170.55, 164.21,
42.24, 140.12, 139.78, 133.21, 132.66, 129.67, 128.77, 128.49,
2
(
.4.5. 3b-Acetoxyl-5-en-16-(2-chlorobenzylidene) – androstano-17-
2-amino-1-cyano-2-oxoethy-lidene) (4e)
Yellow solid, yield 81%, mp 227.4–228.0 °C. H NMR (400 MHz,
CDCl ): d 7.55 (s, 1H, ArH), 7.45 (d, J = 7.2 Hz, 1H, ArH), 7.38 (t,
J = 6.2 Hz, 1H, ArH), 7.33–7.17 (m, 2H, ArH and Ar–CH=, over-
lapped), 6.14 (m, 2H, –NH ), 5.35 (s, 1H, 6-H), 4.70–4.50 (m, 1H,
-H), 2.03 (s, 3H, –OCOCH ), 1.10 (s, 3H, 18-H), 1.05 (s, 3H, 19-
H). C NMR (100 MHz, CDCl ): d 173.27, 170.54, 164.76, 140.02,
39.50, 134.67, 131.61, 129.84, 129.70, 129.61, 126.60, 121.59,
1
1
3
3
(
4
2
2
a
3
2
1
3
(s, 3H, 18-H). C NMR (100 MHz, CDCl
3
3
a
3
1
1
3
2
1
3
3
21.46, 117.68, 115.83, 112.96, 100.84, 73.67, 52.28, 49.42, 47.31,
8.03, 36.77, 36.60, 34.68, 31.41, 31.26, 29.70, 27.64, 21.41,
1
1
3
1
5
16.17, 99.69, 73.69, 52.37, 49.44, 47.33, 38.02, 36.77, 36.59,
35 3 3
1.03, 19.30, 16.63. HRMS (ESI): m/z calcd. for C32H N NaO
4.68, 31.37, 31.25, 30.96, 29.69, 27.64, 21.41, 21.06, 19.28,
+
(
M + Na) , 532.2576; found, 532.2578.
+
6.60. HRMS (ESI): m/z calcd. for C31
H35ClN
2
NaO
3
(M + Na) ,
41.2234; found, 541.2232.
2
(
.4.6. 3b-Acetoxyl-5-en-16-(3-methoxylbenzylidene)-androstano-17-
2-amino-1-cyano-2-oxo ethylidene) (4f)
Yellow solid, yield 90%, mp 146.1–147.8 °C. H NMR (400 MHz,
CDCl ) d 7.28 (m, 1H, ArH), 7.20 (s, 1H, Ar–CH=), 7.01 (d, J = 7.6 Hz,
H, ArH), 6.93 (s, 1H, ArH), 6.86 (d, J = 8.2 Hz, 1H, ArH), 6.37 (s, 2H,
NH ), 5.39 (d, J = 4.3 Hz, 1H, 6-H), 4.69–4.51 (m, 1H, 3 -H), 3.81 (s,
H, –OCH ), 2.03 (s, 3H, –OCOCH ), 1.04 (s, 6H, 18-H and H-19).
): d 174.67, 170.63, 165.60, 159.59, 140.00,
37.85, 137.55, 135.31, 129.60, 122.40, 121.66, 116.36, 115.29,
2.4.8. 3b-Acetoxyl-5-en-16-(2, 4-difluorobenzylidene)-androstano-
17-(2-amino-1-cyano-2-oxo-ethylidene) (4h)
1
1
Yellow solid, yield 85%, mp 143.2–145.5 °C. H NMR (400 MHz,
3
CDCl
NH ), 5.40 (d, J = 4.6 Hz, 1H, 6-H), 4.60 (m, 1H, 3
–OCOCH ), 1.05 (s, 3H, 18-H), 1.04 (s, 3H, 19-H).
(10.0 MHz, CDCl ): d 174.28, 170.64, 165.23, 151.45, 148.96,
3
) d 7.20 (m, 4H, ArH and Ar–CH=, overlapped), 6.38 (s, 2H, –
1
–
3
2
a
-H), 2.04 (s, 3H,
13
2
a
3
C NMR
1
3
3
3
C
3
NMR (100 MHz, CDCl
3
140.04, 138.41, 133.56, 132.96, 126.54, 121.55, 118.12, 117.94,
117.62, 117.45, 116.21, 99.23, 77.40, 77.08, 76.77, 52.36, 49.43,
47.10, 38.00, 36.76, 36.57, 34.69, 31.42, 31.24, 31.21, 27.62,
1
1
3
14.38, 98.80, 73.75, 55.32, 52.40, 49.44, 47.02, 38.02, 36.67,
4.69, 31.33, 29.68, 27.63, 21.41, 21.06, 19.28, 16.48. HRMS (ESI):
21.40, 21.05, 19.27, 16.49. HRMS (ESI): m/z calcd. for C31
(M + H) , 521.2616; found, 521.2614.
H
35
F
2
N
2
O
3
+
+
m/z calcd. for C32
H
38
N
2
NaO
4
(M + Na) , 537.2729; found, 537.2740.
NC
CN
O
O
i
ii
HO
AcO
AcO
3
2
1
O
NC
NH2
iii
R
AcO
4a-k
2 3 4
Scheme 1. Synthesis of steroidal dienamides (4a–k). Reagents and conditions: (i) (Ac) O, DMAP, Et N, DCM, r.t; (ii) malononitrile, NH OAc, EtOH, reflux; (iii) Aldehydes,
NaOAc, EtOH, reflux.