J. Ruiz et al. / Tetrahedron 61 (2005) 3311–3324
3317
125.1, 126.2, 128.2, 128.3, 128.9, 139.1, 140.8, 163.4. MS
(EI) m/z (rel intensity) 383 (MCC1, 8), 382 (MC, 39), 282
(15), 256 (13), 255 (70), 217 (28), 184 (25), 183 (100), 182
(42), 156 (29), 155 (19), 154 (22), 127 (13), 100 (16), 91
(12), 90 (37), 89 (17), 72 (34). Anal. Calcd for C16H19IN2O:
C, 50.28; H, 5.01; N, 7.33. Found: C, 49.99; H, 5.10; N,
7.29.
(29), 200 (12), 150 (18), 107 (15), 100 (36), 94 (11), 92 (15),
85 (10), 83 (13), 79 (10), 77 (20), 72 (56), 64 (14), 63 (13),
56 (14), 51 (12). Anal. Calcd for C18H23IN2O3: C, 48.88; H,
5.24; N, 6.33. Found: C, 48.60; H, 5.36; N, 6.24.
3.3.5. 1-(6-Iodo-2,3-dimethoxybenzyl)pyrrole-2-car-
boxylic acid diethyl amide (5e). According to the general
procedure, N,N-diethyl-pyrrole-2-carboxamide 4a (600 mg,
3.6 mmol) was treated with KOH (780 mg, 13.9 mmol) in
DMSO (15 mL), and a mixture of bromides 3e/3e0 in a 2:1
ratio (2.5 g, 7 mmol). After work-up, flash column chroma-
tography (silicagel, 30% hexane/AcOEt) afforded 5e as a
3.3.2. 1-(2-Iodo-4,5-dimethylbenzyl)pyrrole-2-car-
boxylic acid diethyl amide (5b). According to the general
procedure, N,N-diethyl-pyrrole-2-carboxamide 4a (260 mg,
1.6 mmol) was treated with KOH (340 mg, 6.1 mmol) in
DMSO (6 mL), and bromide 3b (1.03 g, 3.2 mmol). After
work-up, flash column chromatography (silicagel, 20%
hexane/AcOEt) afforded 5b as a colourless oil (530 mg,
1
colourless oil (400 mg, 25%); IR (CHCl3) 1613 cmK1; H
NMR (CDCl3) 1.23 (t, JZ7.1 Hz, 6H), 3.57 (q, JZ7.1 Hz,
4H), 3.68 (s, 3H), 3.81 (s, 3H), 5.39 (s, 2H), 5.97 (dd, JZ
4.0, 2.8 Hz, 1H), 6.29 (dd, JZ4.0, 1.6 Hz, 1H), 6.49 (dd,
JZ2.8, 1.6 Hz, 1H), 6.64 (d, JZ8.7 Hz, 1H), 7.51 (d, JZ
8.7 Hz, 1H); 13C NMR (CDCl3) 13.5, 41.9, 50.5, 55.7, 60.8,
89.6, 106.6, 110.0, 114.1, 123.1, 126.7, 133.5, 134.5, 148.6,
153.1, 164.0. MS (EI) m/z (rel intensity) 442 (MC, 16), 262
(15), 87 (11), 85 (64), 83 (100), 72 (13). Anal. Calcd for
C18H23IN2O3: C, 48.88; H, 5.24; N, 6.33. Found: C, 49.03;
H, 4.89; N, 5.90.
1
83%); IR (CHCl3) 1618 cmK1; H NMR (CDCl3) 1.11 (t,
JZ7.1 Hz, 6H), 2.09 (s, 3H), 2.13 (s, 3H), 3.45 (q, JZ
7.1 Hz, 4H), 5.25 (s, 2H), 6.09 (dd, JZ4.0, 2.8 Hz, 1H),
6.35 (dd, JZ4.0, 2.0 Hz, 1H), 6.59 (s, 1H), 6.72 (dd, JZ2.8,
2.0 Hz, 1H), 7.55 (s, 1H); 13C NMR (CDCl3) 13.5, 18.8,
19.4, 41.3, 55.6, 94.4, 107.0, 110.9, 124.9, 126.1, 129.9,
139.8, 136.9, 137.9, 163.6. MS (EI) m/z (rel intensity) 410
(MC, 17), 284 (23), 283 (100), 245 (31), 212 (17), 211 (57),
210 (44), 196 (17), 190 (17), 184 (19), 183 (13), 168 (12),
119 (10), 118 (23), 117 (17), 115 (13), 100 (17), 91 (12), 85
(10), 83 (16), 72 (29). Anal. Calcd for C18H23IN2O: C,
52.69; H, 5.65; N, 6.83. Found: C, 52.44; H, 5.21; N, 7.02.
3.3.6. 1-(2-Iodo-4,5-methylendioxybenzyl)pyrrole-2-car-
boxylic acid diethyl amide (5f). According to the general
procedure, N,N-diethyl-pyrrole-2-carboxamide 4a (710 mg,
4.3 mmol) was treated with KOH (1.05 g, 18.7 mmol) in
DMSO (6 mL), and bromide 3f (2.9 g, 8.6 mmol). After
work-up, flash column chromatography (silicagel, 30%
hexane/AcOEt) afforded 5f as a colourless oil (1.53 mg,
3.3.3. 1-(2-Iodo-5-methoxybenzyl)pyrrole-2-carboxylic
acid diethyl amide (5c). According to the general
procedure,
N,N-diethyl-pyrrole-2-carboxamide
4a
1
84%); IR (CHCl3) 1615 cmK1; H NMR (CDCl3) 1.14 (t,
(150 mg, 0.9 mmol) was treated with KOH (250 mg,
4.4 mmol) in DMSO (5 mL), and bromide 3c (610 mg,
1.9 mmol). After work-up, flash column chromatography
(silicagel, 30% hexane/AcOEt) afforded 5c as a colourless
JZ7.1 Hz, 6H), 3.46 (q, JZ7.1 Hz, 4H), 5.22 (s, 2H), 5.89
(s, 2H), 6.10 (dd, JZ4.0, 2.8 Hz, 1H), 6.34 (s, 1H), 6.36 (dd,
JZ4.0, 1.6 Hz, 1H), 6.73 (dd, JZ2.8, 1.6 Hz, 1H), 7.19 (s,
1H); 13C NMR (CDCl3) 13.2, 41.0, 55.7, 85.4, 101.3, 107.0,
108.5, 110.8, 118.0, 124.6, 125.7, 134.0, 147.3, 148.3,
163.1. MS (EI) m/z (rel intensity) 426 (MC, 2), 299 (45),
261 (23), 227 (15), 226 (16), 206 (9), 100 (9), 87 (13), 85
(69), 83 (100), 76 (11), 72 (13). Anal. Calcd for
C17H19IN2O3: C, 47.90; H, 4.49; N, 6.57. Found: C,
48.01; H, 4.65; N, 6.12.
oil (350 mg, 94%); IR (CHCl3) 1617 cmK1 1H NMR
;
(CDCl3) 1.10 (t, JZ7.1 Hz, 6H), 3.45 (q, JZ7.1 Hz, 4H),
3.64 (s, 3H), 5.27 (s, 2H), 6.12 (dd, JZ3.6, 2.8 Hz, 1H),
6.26 (d, JZ2.8 Hz, 1H), 6.38 (dd, JZ3.6, 1.6 Hz, 1H),
6.50–6.52 (m, 1H), 6.73 (dd, JZ2.8, 1.6 Hz, 1H), 7.63 (d,
JZ8.7 Hz, 1H); 13C NMR (CDCl3) 13.4, 41.3, 55.1, 56.1,
85.8, 107.2, 111.1, 114.5, 125.1, 126.1, 139.5, 141.9, 160.0,
163.3. MS (EI) m/z (rel intensity) 412 (MC, 3), 286 (24),
285 (100), 214 (14), 213 (41), 212 (23), 192 (23), 186 (13),
170 (17), 120 (15), 100 (14), 85 (23), 83 (39), 72 (20). Anal.
Calcd for C17H21IN2O2: C, 49.52; H, 5.13; N, 6.79. Found:
C, 49.23; H, 5.41; N, 6.59.
3.3.7. 1-(2-Iodo-3,4,5-trimethoxybenzyl)pyrrole-2-car-
boxylic acid diethyl amide (5g). According to the general
procedure, N,N-diethyl-pyrrole-2-carboxamide 4a (150 mg,
0.9 mmol) was treated with KOH (240 mg, 4.3 mmol) in
DMSO (6 mL), and bromide 3g (700 mg, 1.8 mmol). After
work-up, flash column chromatography (silicagel, 30%
hexane/AcOEt) afforded 5g as a colourless oil (240 mg,
3.3.4. 1-(2-Iodo-4,5-dimethoxybenzyl)pyrrole-2-car-
boxylic acid diethyl amide (5d). According to the general
procedure, N,N-diethyl-pyrrole-2-carboxamide 4a (884 mg,
2.0 mmol) was treated with KOH (448 mg, 8.0 mmol) in
DMSO (20 mL), and bromide 3d (1.5 g, 4.2 mmol). After
work-up, flash column chromatography (silicagel, 40%
hexane/AcOEt) afforded 5d as a colourless oil (1.72 mg,
1
56%); IR (CHCl3) 1618 cmK1; H NMR (CDCl3) 1.09 (t,
JZ7.1 Hz, 6H), 3.43 (q, JZ7.1 Hz, 4H), 3.63 (s, 3H), 3.78
(s, 3H), 3.81 (s, 3H), 5.27 (s, 2H), 6.08–6.10 (m, 1H), 6.15
(s, 1H), 6.34–6.36 (m, 1H), 6.73 (broad s, 1H); 13C NMR
(CDCl3) 13.4, 41.4, 55.7, 56.2, 60.6, 60.7, 85.4, 107.1,
107.8, 111.0, 125.0, 126.1, 136.4, 141.0, 152.6, 153.6,
163.2. MS (EI) m/z (rel intensity) 346 (12), 345 (38), 307
(16), 252 (48), 181 (24), 100 (18), 87 (12), 85 (72), 83 (100),
72 (25). Anal. Calcd for C19H25IN2O4: C, 48.32; H, 5.33; N,
5.93. Found: C, 48.17; H, 5.01; N, 5.12.
1
73%); IR (CHCl3) 1616 cmK1; H NMR (CDCl3) 1.11 (t,
JZ7.1 Hz, 6H), 3.44 (q, JZ7.1 Hz, 4H), 3.68 (s, 3H), 3.80
(s, 3H), 5.24 (s, 2H), 6.08–6.09 (m, 1H), 6.34 (dd, JZ3.6,
1.5 Hz, 1H), 6.44 (s, 1H), 6.72 (dd, JZ2.5, 1.5 Hz, 1H),
7.17 (s, 1H); 13C NMR (CDCl3) 13.5, 41.2, 55.6, 55.6, 56.0,
86.1, 107.1, 111.0, 111.9, 121.3, 124.8, 126.2, 133.2, 148.7,
149.4, 163.5. MS (EI) m/z (rel intensity) 442 (MC, 2), 316
(21), 315 (100), 277 (62), 244 (22), 243 (22), 242 (33), 222
3.3.8. 1-(2-Iodobenzyl)pyrrole-2-carboxylic acid meth-
oxy methyl amide (6a). According to the general