Journal of Medicinal Chemistry
Article
n-hexane = 1:1 as eluent) to give 56 (0.18 g, 42%), mp 120−125 °C
(from ethanol/n-hexane). 1H NMR (CDCl3): δ 3.92 (s, 6H), 3.95
(s, 3H), 6.37−6.39 (m, 1H), 6.96−6.98 (m, 1H), 7.16−7.17 (m, 1H), 7.22
(s, 2H), 7.33−7.35 (m, 2H), 7.39−7.47 ppm (m, 3H). IR: ν 1637 cm−1.
Anal. (C20H19NO4 (337.37)) C, H, N. Further elution with the same
eluent furnished 4 (0.19 g, 43%), mp 88−90 °C (from ethanol/
n-hexane). 1H NMR (CDCl3): δ 3.94 (s, 6H), 3.96 (s, 3H), 6.89−6.90
(m, 1H), 7.14−7.16 (m, 1H), 7.19 (s, 2H), 7.36−7.40 (m, 1H), 7.44−
7.46 (m, 2H), 7.49−7.51 (m, 2H), 7.67−7.69 ppm (m, 1H). IR: ν
1621 cm−1. Anal. (C20H19NO4 (337.37)) C, H, N.
(s, 6H), 6.84−6.85 (m, 1H), 7.16 (s, 2H), 7.72−7.73 (m, 1H), 7.80
(t, J = 8.2 Hz, 1H), 8.17−8.26 (m, 3H), 8.53−8.54 ppm (m, 1H). IR:
ν 1640 cm−1. Anal. (C20H18N2O6 (382.37)) C, H, N.
(1-(4-Nitrophenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
methanone (20). Obtained as 4 from 1-(4-nitrophenyl)-1H-pyrrole.
Yield 68%, mp 175−185 °C (from ethanol/n-hexane). 1H NMR
(DMSO-d6): δ 3.78 (s, 3H), 3.88 (s, 6H), 6.87−6.88 (m, 1H), 7.15
(s, 2H), 7.76−7.77 (m, 1H), 8.07 (d, J = 9.2 Hz, 2H), 8.25−8.26
(m, 1H), 8.34 ppm (d, J = 9.2 Hz, 2H). IR: ν 1633 cm−1. Anal.
(C20H18N2O6 (382.37)) C, H, N.
(1-(2-Tolyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone
(32). Obtained as 4 from 66. Yield 71%, mp 120−125 °C (from
ethanol/n-hexane). 1H NMR (DMSO-d6): δ 2.24 (s, 3H), 3.75
(s, 3H), 3.82 (s, 6H), 6.74−6.76 (m, 1H), 7.12−7.14 (m, 3H), 7.35−
7.43 (m, 4H), 7.64−7.66 ppm (m, 1H). IR: ν 1632 cm−1. Anal.
(C21H21NO4 (351.40)) C, H, N.
(1-Methyl-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone
(10). Obtained as 4 from 1-methyl-1H-pyrrole. Yield 16%, mp 130−
1
135 °C (from ethanol/n-hexane). H NMR (CDCl3): δ 3.30 (s, 3H),
3.93 (s, 6H), 3.94 (s, 3H), 6.66−6.68 (m, 1H), 6.69−6.71 (m, 1H),
7.13 (s, 2H), 7.25−7.27 ppm (m, 1H). IR: ν 1610 cm−1. Anal.
(C15H17NO4 (275.30)) C, H, N.
(1-(3-Tolyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone
(33). Obtained as 4 from 67. Yield 80%, mp 105−109 °C (from
ethanol/n-hexane). 1H NMR (DMSO-d6): δ 1.28 (s, 3H), 130 (s, 3H),
3.77 (s, 3H), 3.86 (s, 6H), 4.73−7.81 (m, 1H), 6.77 (s, 1H), 6.89 (d,
J = 7.3 Hz, 1H), 7.14 (s, 2H), 7.23−7.25 (m, 2H), 7.34−7.38 (m, 1H),
7.55 (s, 1H), 8.06 ppm (s, 1H). IR: ν 1712 cm−1. Anal. (C23H25NO5
(395.45)) C, H, N.
Phenyl(1-phenyl-1H-pyrrol-3-yl)methanone (11). Obtained as 4
1
from 1-phenyl-H-pyrrole. Yield 29%. H NMR (CDCl3): δ 6.89−6.91
(m, 1H), 7.11 7.13 (m, 1H), 7.32−7.36 (m, 1H), 7.41−7.49 (m, 6H),
7.51−7.53 (m, 1H), 7.61−7.64 (m, 1H), 7.89−7.93 ppm (m, 2H). IR:
ν 1630 cm−1.22
(1-(2-Chlorophenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
methanone (12). Obtained as 4 from 63. Yield 10%, mp 115−117 °C
1
(1-(4-Tolyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone
(from ethanol/n-hexane). H NMR (CDCl3): δ 3.93 (s, 6H), 3.94
(34). Obtained as 4 from 68. Yield 62%, mp 100−105 °C (from
(s, 3H), 6.90−6.91 (m, 1H), 6.94−6.95 (m, 1H), 7.21 (s, 2H), 7.39−
7.41 (m, 3H), 7.49−7.51 (m, 1H), 7.56−7.59 ppm (m, 1H). IR:
ν 1633 cm−1. Anal. (C20H18ClNO4 (371.81)) C, H, Cl, N.
1
ethanol/n-hexane). H NMR (DMSO-d6): δ 2.35 (s, 3H), 3.76 (s,
3H), 3.86 (s, 6H), 6.77−6.78 (m, 1H), 7.13 (s, 2H), 7.30 (d, J = 8.2 Hz,
2H), 7.50 (t, J = 2.8 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.97−7.98 ppm
(m, 1H). IR: ν 1632 cm−1. Anal. (C21H21NO4 (351.40)) C, H, N.
(1-(2-Methoxyphenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
methanone (35). Obtained as 4 from 69. Yield 25%, mp 120−123 °C
(from ethanol/n-hexane). 1H NMR (CDCl3): δ 3.89 (s, 3H), 3.94 (S,
9H), 6.85−6.87 (m, 1H), 7.01−7.02 (dd, J = 2.1 and 3.0 Hz, 1H),
7.06−7.09 (m, 2H), 7.20 (s, 2H), 7.33−7.39 (m, 2H), 7.58 ppm (t, J =
2.0 Hz, 1H). IR: ν 1633 cm−1. Anal. (C21H21NO5 (367.40)) C, H, N.
(1-(3-Methoxyphenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
methanone (36). Obtained as 4 from 70. Yield 10%. 1H NMR
(DMSO-d6): δ 3.77 (s, 3H), 3.84 (s, 3H), 3.86 (s, 6H), 6.78−6.79
(m, 1H), 6.91−6.93 (m, 1H), 7.14 (s, 2H), 7.27−7.29 (m, 2H), 7.38−
7.42 (m, 1H), 7.55−7.56 (m, 1H), 8.07 ppm (t, J = 2.1 Hz, 1H). IR:
ν 1633 cm−1. Anal. (C21H21NO5 (367.40)) C, H, N.
(1-(3-Chlorophenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
methanone (13). Obtained as 4 from 64. Yield 16%, mp 110−115 °C
1
(from ethanol/n-hexane). H NMR (CDCl3): δ 3.94 (s, 6H), 3.95
(s, 3H), 6.88−6.89 (m, 1H), 7.12 (dd, J = 2.3 and 3.1 Hz, 1H), 7.18
(s, 2H), 7.33−7.36 (m, 2H), 7.41−7.46 (m, 2H), 7.65−7.66 ppm
(m, 1H). IR: ν 1616 cm−1. Anal. (C20H18ClNO4 (371.81)) C, H, Cl, N.
(1-(4-Chlorophenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
methanone (14). Obtained as 4 from 1-(4-chlorophenyl)-1H-pyrrole.
Yield 14%, mp 125−128 °C (from ethanol/n-hexane). 1H NMR
(CDCl3): δ 3.94 (s, 6H), 3.95 (S, 3H), 6.8−6.88 (m, 1H), 7.00 (t, J =
2.7 Hz, 1H), 7.20 (s, 2H), 7.37−7.40 (m, 2H), 7.45−7.49 (m, 2H),
7.64 ppm (t, J = 2.1 Hz, 1H). IR: ν 1636 cm−1. Anal. (C20H18ClNO4
(371.81)) C, H, Cl, N.
(1-(2-Fluorophenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
methanone (15). Obtained as 4 from 1-(2-fluorophenyl)-1H-pyrrole.
Yield 54%, mp 119−121 °C (from ethanol/n-hexane). 1H NMR
(DMSO-d6): δ 3.76 (s, 3H), 3.86 (s, 6H), 6.80−6.81 (m, 1H), 7.14
(s, 2H), 7.32−7.39 (m, 2H), 7.46−7.51 (m, 2H), 7.70 (t, J = 7.8 Hz,
1H), 7.84−7.85 ppm (m, 1H). IR: ν 1633 cm−1. Anal. (C20H18FNO4
(355.36)) C, H, F, N.
(1-(3-Fluorophenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
methanone (16). Obtained as 4 from 1-(3-fluorophenyl)-1H-pyrrole.
Yield 70%, mp 107−114 °C (from ethanol/n-hexane). 1H NMR
(DMSO-d6): δ 3.77 (s, 3H), 3.87 (s, 6H), 6.80−6.82 (m, 1H), 7.14
(s, 2H), 7.16−7.21 (m, 1H), 7.51−7.57 (m, 1H), 7.61−7.63 (m, 2H),
7.71−7.75 (m, 1H), 8.13−8.15 ppm (m, 1H). IR: ν 1706 cm−1. Anal.
(C20H18FNO4 (355.36)) C, H, F, N.
(1-(4-Fluorophenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
methanone (17). Obtained as 4 from 1-(4-fluorophenyl)-1H-pyrrole.
Yield 54%, mp 140−144 °C (from ethanol/n-hexane). 1H NMR
(DMSO-d6): δ 3.76 (s, 3H), 3.86 (s, 6H), 6.78−6.79 (m, 1H), 7.13
(s, 2H), 7.36 (t, J = 2.6 Hz, 2H), 7.50−7.52 (m, 1H), 7.76−7.79
(m, 2H), 8.00−8.02 ppm (m, 1H). IR: ν 1634 cm−1. Anal.
(C20H18FNO4 (355.36)) C, H, F, N.
(1-(4-Methoxyphenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
methanone (37). Obtained as 4 from 1-(4-methoxyphenyl)-1H-
1
pyrrole. Yield 58%, mp 140−145 °C (from ethanol/n-hexane). H
NMR (DMSO-d6): δ 3.76 (s, 3H), 3.81 (s, 3H), 3.86 (s, 6H), 6.76−
6.77 (m, 1H), 7.03−7.07 (m, 2H), 7.13 (s, 2H), 7.42−7.43 (m, 1H),
7.61−7.65 (m, 2H), 7.92−793 ppm (m, 1H). IR: ν 1632 cm−1. Anal.
(C21H21NO5 (367.40)) C, H, N.
(1-(2-Isopropoxyphenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
methanone (38). Obtained as 4 from 71. Yield 42%, mp 130−133 °C
1
(from ethanol/n-hexane). H NMR (DMSO-d6): δ 0.98 (s, 3H), 0.99
(s, 3H), 3.77 (s, 3H), 3.82 (s, 6H), 4.40−4.46 (m, 1H), 6.36 (t, J = 3.2
Hz, 1H), 6.83−6.85 (m, 1H), 7.11 (s, 2H), 7.21−7.27 (m, 2H), 7.37
(t, J = 7.7 Hz, 1H), 7.45 (d, J = 7.8 Hz, 1H), 7.70−7.072 ppm
(m, 1H). IR: ν 1618 cm−1. Anal. (C23H25NO5 (395.45)) C, H, N.
(1-(3-Isopropoxyphenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
1
methanone (39). Obtained as 4 from 72. Yield 35% as a slurry. H
NMR (DMSO-d6): δ 1.28 (s, 3H), 130 (s, 3H), 3.77 (s, 3H), 3.86
(s, 6H), 4.73−7.81 (m, 1H), 6.77 (s, 1H), 6.89 d, J = 7.3 Hz, 1H), 7.14
(s, 2H), 7.23−7.25 (m, 2H), 7.34−7.38 (m, 1H), 7.55 (s, 1H), 8.06
ppm (s, 1H). IR: ν 1634 cm−1. Anal. (C23H25NO5 (395.45)) C, H, N.
(1-(4-Isopropoxyphenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
methanone (40). Obtained as 4 from 73. Yield 63%, mp 99−100 °C
(1-(2-Nitrophenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
methanone (18). Obtained as 4 from 1-(2-nitrophenyl)-1H-pyrrole.
Yield 40%, mp 150−155 °C (from ethanol/n-hexane). 1H NMR
(DMSO-d6): δ 3.75 (s, 3H), 3.86 (s, 6H), 6.78−6.79 (m, 1H), 7.09
(s, 2H), 7.20−7.21 (m, 1H), 7.70−7.79 (m, 3H), 7.86−7.91 (m, 1H),
8.17 ppm (dd, J = 1.4 and 8.2 Hz, 1H). IR: ν 1635 cm−1. Anal.
(C20H18N2O6 (382.37)) C, H, N.
1
(from ethanol/n-hexane). H NMR (DMSO-d6): δ 1.28 (s, 3H), 1.29
(s, 3H), 3.76 (s, 3H), 3.86 (s, 6H), 4.63−4.69 (m, 1H), 6.74−6.76
(m, 1H), 7.02 (d, J = 8.9 Hz, 2H), 7.13 (s, 2H), 7.42−7.43 (m, 1H),
7.59 (d, J = 8.9 Hz, 2H), 7.90−7.92 ppm (m, 1H). IR: ν 1629 cm−1.
Anal. (C23H25NO5 (395.45)) C, H, N.
(1-(3-Nitrophenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)-
( 1 - ( 3 - ( B e n z y l o x y ) p h e n y l ) - 1 H - p y r r o l - 3 - y l ) ( 3 , 4 , 5 -
methanone (19). Obtained as 4 from 65. Yield 46%, mp 145−150 °C
trimethoxyphenyl)methanone (41). Obtained as 4 from 74. Yield
1
1
(from ethanol/n-hexane). H NMR (DMSO-d6): δ 3.78 (s, 3H), 3.87
12% as a slurry. H NMR (DMSO-d6): δ 3.77 (s, 3H), 3.83 (s, 6H),
6546
dx.doi.org/10.1021/jm500561a | J. Med. Chem. 2014, 57, 6531−6552