6186
J. Ruiz et al. / Tetrahedron 62 (2006) 6182–6189
general procedure, N-methoxy-N-methylpyrrole-2-carbox-
amide 2a (308 mg, 2 mmol) was treated with KOH (448 mg,
8 mmol) in DMSO (10 mL), and bromide 1 (1.2 g, 4 mmol).
After work-up, flash column chromatography (silica gel,
30% hexane/AcOEt) afforded 3a as a white solid, that
was crystallised from Et2O (585 mg, 76%): mp (Et2O)
4.4.4. 1-(2-Bromopyridin-3-ylmethyl)pyrrole-2-carbox-
ylic acid diethyl amide (7b). According to the general pro-
cedure, N,N-diethylpyrrole-2-carboxamide 2b (762 mg,
4.49 mmol) was treated with KOH (1.03 g, 18.3 mmol) in
DMSO (10 mL), and bromide 6 (2.3 g, 9.2 mmol). After
work-up, flash column chromatography (silica gel, 30% hex-
ane/AcOEt) afforded 7b as an oil (2.28 mg, 74%): IR (neat)
1616 cmꢀ1; 1H NMR (CDCl3) 1.10 (t, J¼6.7 Hz, 6H), 3.23
(q, J¼6.7 Hz, 4H), 5.33 (s, 2H), 6.14 (dd, J¼4.0, 2.6 Hz,
1H), 6.38 (dd, J¼4.0, 2.0 Hz, 1H), 6.84 (dd, J¼2.6,
1.8 Hz, 1H), 7.04 (dd, J¼7.5, 1.6 Hz, 1H), 7.13 (dd,
J¼7.5, 4.8 Hz, 1H), 8.19 (dd, J¼4.8, 1.6 Hz, 1H); 13C
NMR (CDCl3) 13.4, 41.3, 50.6, 107.7, 111.4, 122.9, 125.1,
126.0, 135.7, 137.0, 141.5, 148.5, 163.0; MS (EI) m/z (rel in-
tensity) 337 (M++2, 43), 335 (M+, 44), 266 (14), 265 (99),
264 (18), 263 (100). Anal. Calcd for C15H18BrN3O: C,
53.58; H, 5.39; N, 12.49. Found: C, 53.46; H, 5.30; N, 12.53.
1
136–138 ꢁC; IR (KBr) 1613 cmꢀ1; H NMR (CDCl3) 3.24
(s, 3H), 3.66 (s, 3H), 5.72 (s, 2H), 6.30 (dd, J¼3.7,
2.6 Hz, 1H), 6.91 (dd, J¼2.6, 1.8 Hz, 1H), 7.10 (dd,
J¼3.7, 1.8 Hz, 1H), 7.14 (s, 1H), 7.44–7.51 (m, 1H),
7.59–7.69 (m, 2H), 7.99 (d, J¼8.5 Hz, 1H); 13C NMR
(CDCl3) 33.4, 52.1, 61.0, 108.8, 117.6, 123.0, 127.1,
127.4, 127.5, 127.8, 128.2, 130.0, 133.4, 134.9, 141.3,
147.4, 161.7; MS (EI) m/z (rel intensity) 375 (M++2, 3),
373 (M+, 6), 316 (20), 315 (97), 314 (21), 313 (100), 264
(28), 223 (16), 222 (82), 221 (14), 220 (88), 209 (12), 208
(13), 207 (63), 206 (17), 205 (17), 178 (11), 176 (30), 141
(20), 140 (33), 103 (21). Anal. Calcd for C17H16BrN3O2:
C, 54.56; H, 4.31; N, 11.23. Found: C, 54.88; H, 4.42;
N, 11.19.
4.4.5. 1-(2-Iodothiophen-3-ylmethyl)pyrrole-2-carbox-
ylic acid methoxy methyl amide (14a). According to the
general procedure, N-methoxy-N-methylpyrrole-2-carbox-
amide 2a (154 mg, 1 mmol) was treated with KOH (224 mg,
4 mmol) in DMSO (5 mL), and bromide 13 (610 mg,
2 mmol). After work-up, flash column chromatography (sil-
ica gel, 20% hexane/AcOEt) afforded 14a as a white solid,
that was crystallised from Et2O (301 mg, 80%): mp (Et2O)
91–92 ꢁC; IR (KBr) 1620 cmꢀ1; 1H NMR (CDCl3) 3.32 (s,
3H), 3.63 (s, 3H), 5.43 (s, 2H), 6.15 (dd, J¼4.0, 2.6 Hz,
1H), 6.60 (d, J¼5.5 Hz, 1H), 6.85 (dd, J¼2.6, 1.8 Hz, 1H),
6.92 (dd, J¼4.0, 1.6 Hz, 1H), 7.34 (d, J¼5.5 Hz, 1H); 13C
NMR (CDCl3) 33.6, 49.0, 60.8, 74.6, 107.9, 116.4, 122.8,
127.0, 127.8, 130.9, 143.1, 162.1; MS (EI) m/z (rel intensity)
376 (M+, 1), 316 (23), 249 (21), 223 (31), 191 (6), 190 (14),
189 (100), 188 (6), 161 (6), 160 (9), 96 (14), 70 (6). Anal.
Calcd for C12H13IN2O2S: C, 38.31; H, 3.48; N, 7.45.
Found: C, 38.26; H, 3.45; N, 7.32.
4.4.2. 1-(2-Bromoquinolin-3-ylmethyl)pyrrole-2-carbox-
ylic acid diethyl amide (3b). According to the general
procedure, N,N-diethylpyrrole-2-carboxamide 2b (336 mg,
2 mmol) was treated with KOH (448 mg, 8 mmol) in
DMSO (10 mL), and bromide 1 (1.2 g, 4 mmol). After
work-up, flash column chromatography (silica gel, 30% hex-
ane/AcOEt) afforded 3b as a white solid, that was crystal-
lised from Et2O (585 mg, 76%): mp (Et2O) 136–138 ꢁC;
IR (KBr) 1615 cmꢀ1; 1H NMR (CDCl3) 1.02 (t, J¼6.7 Hz,
6H), 3.38 (q, J¼6.7 Hz, 4H), 5.48 (s, 2H, CH2), 6.16 (dd,
J¼3.8, 2.8 Hz, 1H), 6.42 (d, J¼2.8, 1.6 Hz, 1H), 6.82 (br
s, 1H), 7.43–7.48 (m, 2H), 7.60–7.65 (m, 2H), 7.95 (d,
J¼8.7 Hz, 1H); 13C NMR (CDCl3) 13.4, 40.9, 51.0, 107.6,
111.6, 125.4, 125.8, 127.1, 127.2, 127.5, 128.1, 130.2,
132.5, 136.4, 141.8, 147.4, 163.1; MS (EI) m/z (rel intensity)
387 (M++2, 47), 385 (M+, 46), 316 (8), 315 (42), 314 (17),
313 (42), 312 (10), 307 (18), 306 (79), 305 (7), 286 (17),
285 (17), 235 (10), 234 (22), 233 (72), 223 (14), 222 (97),
221 (16), 220 (100), 207 (75), 206 (30), 205 (46), 141
(40), 140 (66), 115 (7), 114 (15), 113 (10), 103 (14), 100
(16), 72 (20). Anal. Calcd for C19H20BrN3O: C, 59.08; H,
5.22; N, 10.88. Found: C, 59.18; H, 5.53; N, 10.56.
4.4.6. 1-(2-Iodothiophen-3-ylmethyl)pyrrole-2-carbox-
ylic acid diethyl amide (14b). According to the general pro-
cedure, N,N-diethylpyrrole-2-carboxamide 2b (225 mg,
1.3 mmol) was treated with KOH (304 mg, 5.4 mmol) in
DMSO (5 mL), and bromide 13 (821 mg, 2.7 mmol). After
work-up, flash column chromatography (silica gel, 30% hex-
ane/AcOEt) afforded 14b as an oil (305 mg, 58%): IR (KBr)
1609 cmꢀ1; 1H NMR (CDCl3) 1.14 (t, J¼7.1 Hz, 6H), 3.45
(q, J¼7.1 Hz, 4H), 5.22 (s, 2H), 6.09 (d, J¼2.8 Hz, 1H), 6.34
(dd, J¼2.8, 1.6 Hz, 1H), 6.63 (d, J¼5.5 Hz, 1H), 6.81 (d,
J¼1.6 Hz, 1H), 7.33 (d, J¼5.5 Hz, 1H); 13C NMR
(CDCl3) 13.5, 40.9, 48.3, 75.0, 107.0, 111.1, 124.8, 125.8,
128.0, 130.9, 143.0, 163.5; MS (EI) m/z (rel intensity) 388
(M+, 5), 262 (19), 261 (100), 223 (41), 190 (16), 189 (52),
188 (18), 168 (92), 162 (13), 160 (14), 100 (11), 97 (16),
96 (24), 94 (10), 72 (33), 70 (15), 56 (11). Anal. Calcd for
C14H17IN2OS: C, 43.31; H, 4.41; N, 7.21. Found: C,
43.22; H, 4.31; N, 7.35.
4.4.3. 1-(2-Bromopyridin-3-ylmethyl)pyrrole-2-carbox-
ylic acid methoxy methyl amide (7a). According to the
general procedure, N-methoxy-N-methylpyrrole-2-carbox-
amide 2a (481 mg, 3.12 mmol) was treated with KOH
(701 mg, 12.5 mmol) in DMSO (10 mL), and bromide 6
(1.6 g, 6.25 mmol). After work-up, flash column chromato-
graphy (silica gel, 30% hexane/AcOEt) afforded 7a as an oil
1
(668 mg, 66%): IR (neat) 1624 cmꢀ1; H NMR (CDCl3)
3.25 (s, 3H), 3.66 (s, 3H), 5.56 (s, 2H), 6.25 (dd, J¼4.0,
2.6 Hz, 1H), 6.78 (dd, J¼7.5, 1.6 Hz, 1H), 6.84 (dd,
J¼2.6, 1.8 Hz, 1H), 7.04 (dd, J¼4.0, 2.0 Hz, 1H), 7.13
(dd, J¼7.5, 4.8 Hz, 1H), 8.22 (dd, J¼4.8, 1.6 Hz, 1H); 13C
NMR (CDCl3) 33.0, 51.4, 60.6, 108.4, 116.7, 122.5, 122.7,
127.5, 135.4, 135.9, 140.6, 147.9, 161.2; MS (EI) m/z (rel in-
tensity) 325 (M++2, 3), 323 (M+, 4), 266 (13), 265 (100), 264
(13), 263 (100), 184 (15), 170 (50), 156 (19), 155 (21). Anal.
Calcd for C13H14BrN3O2: C, 48.16; H, 4.35; N, 12.96.
Found: C, 48.24; H, 4.53; N, 12.85.
4.4.7. 1-(2-Iodothiophen-3-ylmethyl)pyrrole-2-carbox-
ylic acid morpholino amide (14c). According to the general
procedure, 2-morpholinocarbonylpyrrole 2c (163 mg,
0.91 mmol) was treated with KOH (203 mg, 3.62 mmol) in
DMSO (5 mL), and bromide 13 (548 mg, 1.81 mmol).
After work-up, flash column chromatography (silica gel,
20% hexane/AcOEt) afforded 14c as an oil (237 mg,