ˇ
Z. Casar et al. / Tetrahedron 61 (2005) 7508–7519
7515
prepared from compound 3 (1.00 g, 4.09 mmol) and urea
0.74 g, 12.28 mmol) in the presence of HCl37% (3.0 mL,
6.3 mmol) in DMAA (10 mL). Treated with ice-water
100 mL) and quenched with K CO3 (25 mL) saturated
Data for major (E)-isomer 5a. 1470 mg (65%) as light
yellow crystalline powder; mp 145–150 8C (from PhMe/
(
3
(
MeOHZ4:1); IR 3445, 3404, 3314, 2950, 1699, 1634,
K1 1
1601, 1550, 1390, 1208 cm ; H NMR (DMSO-d ) d: 3.63
2
6
0
solution. Extracted with (3!60 mL) AcOEt.
(3H, s, CH ), 7.00 (1H, ddd, JZ8.0, 7.0, 1.1 Hz, H–C(5 )),
3
0
7
.12 (1H, dt, JZ7.2, 1.1 Hz, H–C(6 )), 7.18 (1H, d, JZ
0
0
Data for major (E)-isomer 4a. 619 mg (58%) as white
crystalline powder; mp 136–139 8C (from PhMe/MeOHZ
7.9 Hz, H–C(7 )), 7.32 (1H, d, JZ2.6 Hz, H–C(2 )), 7.42
0
(1H, td, JZ7.9, 1.1 Hz, H–C(4 )), 7.88 (1H, br s, NH), 8.45
K1
4
:1); IR 3349, 3310, 1680, 1642, 1596, 1493, 1248 cm
H NMR (DMSO-d ) d: 3.60 (3H, s, CH ), 6.46 (2H, br s,
;
(1H, br s, NH), 8.70 (1H, d, JZ11.3 Hz, H–C(3)), 9.12
1
13
(1H, d, JZ11.3 Hz, NH), 11.31 (1H, br s, NH); C NMR
6
3
0
NH ), 6.98 (1H, ddd, JZ7.9, 7.0, 1.1 Hz, H–C(5 )), 7.10
(DMSO-d ) d: 52.2, 105.1, 107.1, 112.5, 2!C 119.9, 122.1,
2
6
0
(
7
7
1H, ddd, JZ7.7, 7.0, 1.1 Hz, H–C(6 )), 7.19 (1H, dd, JZ
126.6, 127.6, 137.1, 140.2, 168.6, 182.4; MS (EI) m/z: 275
(MC, 100), 258 (18), 243 (9), 233 (17), 216 (45), 201 (21),
184 (43), 173 (31), 155 (68), 141 (27), 129 (43); HRMS:
found 275.0735, C H N O S, requires 275.0728; Anal.
0
0
.9, 0.8 Hz, H–C(7 )), 7.26 (1H, d, JZ2.6 Hz, H–C(2 )),
0
NH), 11.23 (1H, br s, NH); C NMR (DMSO-d ) d: 51.9,
.41 (1H, td, JZ8.3, 0.8 Hz, H–C(4 )), 8.18 (2H, s, H–C(3),
1
3
6
13 13 3 2
1
1
2
1
2
5
01.3, 107.5, 112.4, 119.7, 120.0, 121.9, 126.2, 127.7,
37.0, 138.3, 155.1, 168.9; MS (EI) m/z: 259 (MC, 100),
42 (26), 227 (30), 216 (42), 184 (87), 155 (72), 141 (23),
29 (61); HRMS: found 259.0963, C H N O , requires
Calcd for C H N O S: C, 56.71; H, 4.76; N, 15.26.
13 13 3 2
Found: C, 56.59; H, 4.88; N, 14.88.
Data for minor (Z)-isomer 5b. 208 mg (9%) as yellow
needles; mp 216–220 8C (from MeOH); IR 3469, 3360,
3285, 3163, 1673, 1638, 1622, 1548, 1385, 1196 cm ; H
1
3 13 3 3
59.0957; Anal. Calcd for C H N O !2/3 CH OH: C,
3
1
3
13
3
3
K1
1
8.49; H, 5.63; N, 14.97. Found: C, 58.17; H, 5.85; N, 14.69.
NMR (DMSO-d ) d: 3.72 (3H, s, CH ), 7.01 (1H, dt, JZ7.2,
6
3
0
0
Data for minor (Z)-isomer 4b. 140 mg (13%) as white
crystals; mp 226–229 8C (from MeOH); IR 3434, 3339,
1.1 Hz, H–C(5 )), 7.10 (1H, dt, JZ6.8, 1.1 Hz, H–C(6 )),
7.34 (1H, d, JZ2.6 Hz, H–C(2 )), 7.39 (1H, d, JZ7.9 Hz,
H–C(7 )), 7.50 (1H, d, JZ7.9 Hz, H–C(4 )), 8.19 (1H, d,
0
K1
1
0
0
3
(
6
1
7
158, 1695, 1646, 1550, 1493, 1206 cm
DMSO-d ) d: 3.67 (3H, s, CH ), 6.94 (2H, br s, NH ),
;
H NMR
JZ10.9 Hz, H–C(3)), 8.67, 8.72 (2H, 2 x br s, NH ), 10.85
6
3
2
2
13
0
.98 (1H, dt, JZ7.2, 1.1 Hz, H–C(5 )), 7.08 (1H, dt, JZ7.2,
.1 Hz, H–C(6 )), 7.26 (1H, d, JZ2.6 Hz, H–C(2 )), 7.34–
.40 (2H, m, H–C(7 ), H–C(4 )), 7.55 (1H, d, JZ11.7 Hz,
(1H, d, JZ11.3 Hz, NH), 11.12 (1H, br s, NH); C NMR
0
0
(DMSO-d ) d: 52.3, 102.2, 107.1, 111.2, 112.5, 119.8,
6
0
0
119.9, 122.0, 125.7, 127.4, 136.8, 141.4, 169.3, 182.3; MS
(EI) m/z: 275 (MC, 100), 258 (12), 243 (14), 233 (14), 216
(43), 201 (22), 184 (42), 173 (28), 155 (50), 141 (23), 129
(35); HRMS: found 275.0735, C H N O S, requires
H–C(3)), 9.93 (1H, d, JZ12.1 Hz, NH), 11.01 (1H, br s,
1
NH); C NMR (DMSO-d ) d: 51.9, 98.8, 111.9, 112.4,
3
6
1
1
19.6, 119.8, 121.8, 125.1, 127.8, 136.8, 140.2, 155.1,
69.5; MS (EI) m/z: 259 (MC, 100), 242 (32), 227 (37), 216
1
3 13 3 2
275.0728; Anal. Calcd for C H N O S: C, 56.71; H,
13 13 3 2
(
2
44), 184 (67), 155 (58), 141 (26), 129 (47); HRMS: found
59.0962, C H N O , requires 259.0957; Anal. Calcd for
C H N O : C, 60.22; H, 5.05; N, 16.21. Found: C, 60.39;
4.76; N, 15.26. Found: C, 56.78; H, 4.89; N, 15.08.
1
3 13 3 3
1
3 13 3 3
5
.2.3. (E)-Methyl 3-(3-ethylureido)-2-(1H-indol-3-yl)
propenoate (6a) and (Z)-methyl 3-(3-ethylureido)-2-
1H-indol-3-yl)propenoate (6b). These compounds were
H, 5.12; N, 16.12.
(
Data for (E,E)-isomer (4c). 150 mg (16%) as white powder;
mp 246–248 8C (from MeOH); IR 3351, 3303, 2953, 1686,
1
(
(
H–C(7 )), 7.22 (1H, d, JZ2.6 Hz, H–C(2 )), 7.33 (1H, d,
JZ7.9 Hz, H–C(4 )), 8.14 (1H, d, JZ11.7 Hz, H–C(3)),
prepared from compound 3 (2.00 g, 8.19 mmol) and
N-ethylurea (2.164 g, 24.56 mmol) in the presence of
HCl37% (6.0 mL, 72.5 mmol) in DMAA (20 mL). Treated
with ice-water (200 mL) and quenched with K CO
2 3
(50 mL) saturated solution. Extracted with (6!50 mL)
AcOEt.
K1 1
643, 1511, 1435, 1194 cm ; H NMR (DMSO-d ) d: 3.62
6
0
3H, s, CH ), 6.94 (1H, dt, JZ7.2, 1.1 Hz, H–C(5 )), 7.05
3
0
1H, dt, JZ7.2, 1.1 Hz, H–C(6 )), 7.14 (1H, d, JZ7.9 Hz,
0
0
0
9
NH); C NMR (DMSO-d ) d: 52.2, 105.3, 106.9, 112.4,
.04 (1H, d, JZ11.7 Hz, NH), 11.20 (1H, d, JZ2.3 Hz,
13
Data for major (E)-isomer 6a. 1600 mg (68%) as white
crystalline powder; mp 212–215 8C (from PhMe/MeOHZ
6
1
1
19.8, 120.0, 122.0, 126.5, 127.5, 136.2, 136.9, 152.1,
68.5; MS (EI) m/z: 458 (MC, 78), 426 (10), 394 (6), 367
4
1
7
3
:1); IR 3355, 2973, 1707, 1676, 1642, 1546, 1430,
214 cm
K1
1
; H NMR (DMSO-d ) d: 0.95 (3H, t, JZ
6
(
(
6), 242 (25), 216 (100), 184 (83), 155 (63), 141 (16), 129
26); HRMS: found 458.1596, C H N O , requires
.1 Hz, CH CH ), 3.02 (2H, dq, JZ7.2, 5.3 Hz, CH CH ),
2
3
2
3
2
5
22
4
5
.58 (3H, s, CH ), 6.85 (1H, br t, JZ5.3 Hz, NH), 6.97 (1H,
3
458.1590; Anal. Calcd for C H N O : C, 65.49; H, 4.84;
25 22 4 5
N, 12.22. Found: C, 65.32; H, 4.93; N, 12.08.
0
dt, JZ7.1, 1.1 Hz, H–C(5 )), 7.09 (1H, dt, JZ7.2, 1.1 Hz,
H–C(6 )), 7.16 (1H, d, JZ7.9 Hz, H–C(7 )), 7.23 (1H, d,
0
0
0
0
JZ2.3 Hz, H–C(2 )), 7.40 (1H, d, JZ8.3 Hz, H–C(4 )),
8.09 (1H, d, JZ12.4 Hz, NH), 8.19 (1H, d, JZ12.4 Hz,
5
.2.2. (E)-Methyl 2-(1H-indol-3-yl)-3-thioureidopro-
1
3
H–C(3)), 11.22 (1H, br s, NH); C NMR (DMSO-d ) d:
penoate (5a) and (Z)-methyl 2-(1H-indol-3-yl)-3-thio-
ureidopropenoate (5b). These compounds were prepared
from compound 3 (2.00 g, 8.19 mmol) and thiourea
6
15.2, 34.5, 51.4, 104.0, 107.0, 111.9, 119.2, 119.5, 121.4,
125.7, 127.2, 136.5, 137.8, 153.7, 168.4; MS (EI) m/z: 287
(MC, 81), 255 (5), 242 (13), 216 (74), 184 (100), 156 (63),
141 (29), 129 (45); HRMS: found 287.1261, C H N O ,
(
7
(
1.870 g, 24.56 mmol) in the presence of HCl37% (6.0 mL,
2.5 mmol) in DMAA (20 mL). Treated with ice-water
200 mL) and quenched with K CO3 (50 mL) saturated
1
5 17 3 3
requires 287.1269; Anal. Calcd for C H N O : C, 62.71;
15 17 3 3
2
solution. Extracted with (6!50 mL) AcOEt.
H, 5.96; N, 14.63. Found: C, 62.80; H, 6.09; N, 14.62.