Journal of Medicinal Chemistry
Article
(s, 2 H), 2.95−2.90 (m, 1 H), 2.35 (s, 3 H), 2.22 (s, 3 H), 0.97 (d, J =
6.6 Hz, 4 H). 13C NMR (125 MHz, DMSO-d6), 174.0, 172.4, 155.6,
147.5, 147.0, 145.4, 142.0, 141.5, 140.0, 138.4, 137.6, 137.4, 136.2,
135.3, 134.4, 131.0, 125.9, 122.2, 118.8, 52.9, 45.9, 42.0, 41.8, 32.4,
25.4, 16.8. LRMS calcd for C26H25N3O4FS (M + H)+, 494.2; found,
494.3.
1-[(2-Amino-4-pyridinyl)methyl]-N-(cyclopropylsulfonyl)-3-
(1,2-dihydro-2-oxo-3-pyridinyl)-5-methyl-1H-indole-2-carbox-
amide (17). Compound 17 was prepared according to the reac-
tion sequence outlined in Scheme 1 and the general procedures
described above for the preparation of generic compound 9. 1H NMR
(500 MHz, DMSO-d6), 13.45 (s, 1 H), 12.84 (s, 2 H), 7.94 (s, 1 H),
7.90 (d, J = 6.6 Hz, 1 H), 7.81 (q, J = 1.9 Hz, 1 H), 7.74 (s, 1 H),
7.45 (d, J = 8.2 Hz, 1 H), 7.24 (s, 2 H), 6.68 (t, J = 6.9 Hz, 1 H), 6.60
(d, J = 7.0 Hz, 1 H), 6.41 (s, 1 H), 5.67 (s, 2 H), 2.98−2.93 (m, 1 H),
2.37 (s, 3 H), 1.01 (d, J = 7.9 Hz, 4 H). 13C NMR (125 MHz, DMSO-
d6), 174.0, 172.1, 167.3, 165.4, 155.8, 147.5, 142.1, 139.9, 139.0, 137.8,
134.1, 131.3, 130.0, 126.2, 122.0, 121.9, 120.4, 119.1, 109.3, 58.6, 42.6,
42.1, 41.8, 33.4, 32.4, 25.3, 16.8. LRMS calcd for C24H24N5O4S
(M + H)+, 478.2; found, 478.3.
6.67−6.62 (m, 1 H), 5.87 (s, 2 H), 3.31 (s, 3 H), 2.93−2.89 (m, 1 H),
2.37 (s, 3 H), 0.97 (s, 4 H). 13C NMR (125 MHz, DMSO-d6), 163.6,
161.8, 161.4, 158.8, 157.0, 152.8, 145.4, 139.5, 137.3, 136.8, 133.1,
131.6, 131.2, 131.1, 128.5, 127.3, 120.8, 116.1, 115.3, 111.9, 111.5,
108.6, 44.0, 43.1, 31.6, 31.3, 21.9, 6.3. LRMS calcd for C27H24N4O6FS2
(M + H)+, 583.1; found, 583.0.
1-[[2-Chloro-5-[(trifluoromethyl)sulfonyl]phenyl]methyl]-N-
(cyclopropylsulfonyl)-3-(1,2-dihydro-2-oxo-3-pyridinyl)-5-
methyl-1H-indole-2-carboxamide (23). Compound 23 was pre-
pared according to the reaction sequence outlined in Scheme 1 and
the general procedures described above for the preparation of generic
1
compound 9. H NMR (500 MHz, DMSO-d6), 13.03 (s, 1 H), 12.88
(s, 1 H), 8.08−8.02 (m, 2 H), 7.84 (dd, J = 1.6, 1.5 Hz, 1 H), 7.76−
7.74 (m, 1 H), 7.50 (d, J = 8.8 Hz, 1 H), 7.24 (s, 1 H), 7.21 (d, J =
8.8 Hz,1 H), 7.06 (d, J = 1.8 Hz, 1 H), 6.68 (t, J = 6.6 Hz, 1 H), 5.87
(s, 2 H), 2.86−2.81 (m, 1 H), 2.37 (s, 3 H), 0.92 (d, J = 6.0 Hz, 4 H).
13C NMR (125 MHz, DMSO-d6), 163.6, 161.7, 156.9, 145.6, 142.4,
140.1, 137.1, 136.8, 133.0, 131.8, 131.6, 131.1, 129.6, 129.4, 128.6, 127.3,
123.5, 120.9, 116.0, 111.4, 109.8, 108.8, 16.6, 31.5, 21.9, 6.2, 5.1. LRMS
calcd for C26H22N3O6ClF3S2 (M + H)+, 628.0; found, 628.3.
1-[(5-Cyano-2-fluorophenyl)methyl]-N-(cyclopropylsulfon-
yl)-3-(1,2-dihydro-2-oxo-3-pyridinyl)-5-methyl-1H-indole-2-
carboxamide (8). Compound 18 was prepared according to the
reaction sequence outlined in Scheme 1 and the general procedures
described above for the preparation of generic compound 9. 1H NMR
(500 MHz, DMSO-d6), 12.73 (s, 1 H), 12.65 (s, 1 H), 7.90−7.86
(m, 1 H), 7.82 (d, J = 6.4 Hz, 1 H), 7.67 (s, 1 H), 7.56−7.49 (s, 2 H),
7.23−7.20 (m, 3 H), 6.61 (t, J = 6.2 Hz, 1 H), 5.76 (s, 2 H), 2.93−2.87
(m, 1 H), 2.37 (s, 3 H), 0.95 (d, J = 7.6 Hz, 4 H). 13C NMR (125 MHz,
DMSO-d6), 164.1, 163.9, 163.4, 162.1, 161.9, 161.5, 146.4, 144.9, 143.8,
140.1, 139.7, 139.4, 136.9, 136.4, 135.3, 134.8, 133.5, 133.2, 131.4, 129.6,
129.4, 128.2, 127.2, 125.8, 123.8, 123.0, 120.8, 118.8, 118.2, 118.1, 115.9,
111.5, 108.7, 108.3, 107.2, 98.3, 42.2, 35.2, 34.8, 32.9, 31.5, 31.3, 30.1,
29.9, 21.9, 6.3, 5.9, 5.1. LRMS calcd for C26H22N4O4FS (M + H)+,
505.1; found, 505.3.
1-[[5-(Aminocarbonyl)-2-fluorophenyl]methyl]-N-(cyclopro-
pylsulfonyl)-3-(1,2-dihydro-2-oxo-3-pyridinyl)-5-methyl-1H-in-
dole-2-carboxamide (19). Compound 19 was prepared according to
the reaction sequence outlined in Scheme 1 and the general proce-
dures described above for the preparation of generic compound 9.
1H NMR (500 MHz, DMSO-d6), 12.82 (s, 1 H), 12.78 (s, 1 H), 7.89
(s, 1 H), 7.84−7.80 (m, 2 H), 7.70 (s, 1 H), 7.55 (d, J = 7.8 Hz, 2 H),
7.38 (s, 1 H), 7.30 (t, J = 9.3 Hz, 1 H), 7.21−7.18 (m, 2 H), 6.65−6.62
(m, 1 H), 5.76 (s, 2 H), 2.96−2.89 (m, 1 H), 2.36 (s, 3 H), 0.96 (d, J =
6.0 Hz, 4 H). 13C NMR (125 MHz, DMSO-d6), 167.6, 163.5, 161.9,
161.5, 152.5, 145.3, 137.2, 136.6, 131.6, 131.1, 130.0, 129.7, 128.1,
127.2, 125.9, 125.8, 125.2, 123.9, 120.7, 116.2, 116.0, 115.6, 111.7, 108.4,
67.9, 42.7, 35.3, 31.6, 31.3, 30.1, 28.9, 16.0, 24.9, 21.9, 6.3. LRMS calcd
for C26H24N4O5FS (M + H)+, 523.1; found, 523.3.
1-[[5-(Aminosulfonyl)-2-fluorophenyl]methyl]-N-(cyclopro-
pylsulfonyl)-3-(1,2-dihydro-2-oxo-3-pyridinyl)-5-methyl-1H-in-
dole-2-carboxamide (21). Compound 21 was prepared according to
the reaction sequence outlined in Scheme 1 and the general proce-
dures described above for the preparation of generic compound 9.
1H NMR (500 MHz, DMSO-d6), 12.84 (s, 2 H), 7.82−7.78 (m, 2 H),
7.73−7.71 (m, 1 H), 7.54 (d, J = 8.1 Hz, 1 H), 7.49−7.43 (m, 2 H),
7.38 (s, 2 H), 7.21 (d, J = 8.8 Hz, 1 H), 7.19 (s, 1 H), 6.66 (t, J = 8.0
Hz, 1 H), 5.78 (s, 2 H), 2.96−2.91 (m, 1 H), 2.36 (s, 3 H), 0.97 (d, J =
6.1 Hz, 4 H). 13C NMR (125 MHz, DMSO-d6), 163.6, 163.2, 161.8,
161.2, 152.3, 145.4, 141.4, 137.3, 136.7, 131.3, 128.5, 127.5, 127.3,
126.9, 125.8, 120.8, 117.3, 115.7, 111.6, 108.6, 67.9, 42.8, 31.6, 31.3,
30.1, 26.0, 21.9. LRMS calcd for C25H24N4O6FS2 (M + H)+, 559.1;
found, 559.3.
1-[[2-Chloro-5-[(trifluoromethyl)sulfinyl]phenyl]methyl]-N-
(cyclopropylsulfonyl)-3-(1,2-dihydro-2-oxo-3-pyridinyl)-5-
methyl-1H-indole-2-carboxamide (24). Compound 24 was pre-
pared according to the reaction sequence outlined in Scheme 1 and
the general procedures described above for the preparation of generic
1
compound 9. H NMR (500 MHz, DMSO-d6), 12.93 (s, 1 H), 12.83
(s,1 H), 7.89 (d, J = 1.6 Hz, 1 H), 7.84−7.81 (m, 1 H), 7.73 (s,1 H),
7.43 (d, J = 8.8 Hz, 1 H), 7.23 (s,1 H), 7.18 (d, J = 8.4 Hz, 1 H), 6.91
(s, 1 H), 6.87 (s, 1 H), 6.71−6.63 (m, 1 H), 5.83 (s, 2 H), 2.88−2.80
(m, 1 H), 2.36 (s, 3 H), 1.35 (d, J = 1.6 Hz, 4 H). 13C NMR (125 MHz,
DMSO-d6), 163.6, 152.3, 145.4, 140.0, 138.8, 137.8, 136.7, 135.5, 131.8,
131.5, 129.6, 128.9, 128.3, 127.3, 127.2, 126.7, 125.8, 125.2, 120.9, 111.5,
108.6, 108.5, 46.6, 35.2, 31.5, 31.3, 30.1, 21.9, 61.2. LRMS calcd for
C26H22N3O5ClF3S2 (M + H)+, 612.1; found, 612.3.
1-[[4-Chloro-2-fluoro-5-(methylsulfonyl)phenyl]methyl]-N-
(cyclopropylsulfonyl)-3-(1,2-dihydro-2-oxo-3-pyridinyl)-5-
methyl-1H-indole-2-carboxamide (26). Compound 26 was pre-
pared according to the reaction sequence outlined in Scheme 1 and
the general procedures described above for the preparation of generic
1
compound 9. H NMR (500 MHz, DMSO-d6), 12.89 (s, 1 H), 12.83
(s, 1 H), 7.87 (d, J = 9.8 Hz, 1 H), 7.81 (d, J = 6.4 Hz, 1 H), 7.76
(d, J = 7.6 Hz, 1 H), 7.72 (s, 1 H), 7.61 (d, J = 8.4 Hz, 1 H), 7.28 (d, J =
8.5 Hz, 1 H), 7.20 (s, 1 H), 6.66 (t, J = 6.7 Hz, 1 H), 5.79 (s, 2 H),
3.31 (s, 3 H), 2.95−2.90 (m, 1 H), 2.67 (q, J = 7.5 Hz, 2 H), 1.18
(t, J = 7.6 Hz, 3 H), 0.99 (d, J = 8.5 Hz, 4 H). 13C NMR (125 MHz,
DMSO-d6), 164.2, 163.5, 162.1, 161.8, 161.4, 157.0, 145.5, 138.1, 137.4,
136.7, 136.3, 135.2, 133.1, 132.1, 129.2, 127.4, 127.1, 126.4, 126.3, 123.6,
120.7, 120.4, 119.5, 116.1, 111.6, 108.7, 43.3, 42.4, 31.6, 29.9, 29.4, 29.0,
17.0, 6.3, 5.9, 5.1. LRMS calcd for C27H26N3O6ClFS2 (M + H)+, 606.1;
found, 606.3.
1-[[4-Cyano-2-fluoro-5-(methylsulfonyl)phenyl]methyl]-N-
(cyclopropylsulfonyl)-3-(1,2-dihydro-2-oxo-3-pyridinyl)-5-
methyl-1H-indole-2-carboxamide (27). Compound 27 was pre-
pared according to the reaction sequence outlined in Scheme 1 and
the general procedures described above for the preparation of generic
1
compound 9. H NMR (500 MHz, DMSO-d6), 12.90 (s, 1 H), 12.85
(s, 1 H), 8.33 (d, J = 9.4 Hz, 1 H), 7.83 (d, J = 5.7 Hz, 1 H), 7.72
(s, 1 H), 7.67 (d, J = 6.7 Hz, 1 H), 7.62 (d, J = 8.8 Hz, 1 H), 7.29 (d, J =
9.0 Hz, 1 H), 7.22 (s, 1 H), 6.66 (s, 1 H), 5.87 (s, 2 H), 3.32 (s, 3 H),
2.90 (s, 1 H), 2.67 (q, J = 7.5 Hz, 2 H), 1.18 (t, J = 7.3 Hz, 3 H), 0.97
(s, 4 H). 13C NMR (125 MHz, DMSO-d6), 163.4, 163.0, 162.4, 161.4,
161.0, 156.4, 155.6, 147.0, 141.3, 140.4, 139.7, 134.4, 132.5, 132.4, 130.9,
130.0, 128.2, 124.5, 124.3, 122.6, 122.0, 121.0, 114.4, 112.6, 85.4, 69.1,
67.0, 63.0, 44.0, 32.9, 29.8, 29.2, 28.3, 24.7, 22.6, 17.2, 6.1, 5.8, 4.7.
LRMS calcd for C28H26N4O6FS2 (M + H)+, 597.1; found, 597.3
1-[[5-(Aminosulfonyl)-2,4-dichlorophenyl]methyl]-N-(cyclo-
propylsulfonyl)-3-(1,2-dihydro-2-oxo-3-pyridinyl)-5-ethyl-1H-
indole-2-carboxamide (28). Compound 28 was prepared according
to the reaction sequence outlined in Scheme 1 and the general proce-
dures described above for the preparation of generic compound 9.
1H NMR (500 MHz, DMSO-d6), 12.87 (s, 2 H), 7.94 (s, 1 H), 7.83
1-[[3-Cyano-2-fluoro-5-(methylsulfonyl)phenyl]methyl]-N-
(cyclopropylsulfonyl)-3-(1,2-dihydro-2-oxo-3-pyridinyl)-5-
methyl-1H-indole-2-carboxamide (22). Compound 22 was
prepared according to the reaction sequence outlined in Scheme 1
and the general procedures described above for the preparation of generic
1
compound 9. H NMR (500 MHz, DMSO-d6), 12.89 (s, 1 H), 12.83
(s, 1 H), 8.32 (d, J = 9.5 HZ, 1 H), 7.82 (q, J = 1.6 Hz, 1 H), 7.72
(s, 1 H), 7.62 (q, J = 6.8 Hz, 2 H), 7.24 (d, J = 8.9 Hz, 1 H), 7.22 (s, 1 H),
2097
dx.doi.org/10.1021/jm201322r | J. Med. Chem. 2012, 55, 2089−2101