2-(4-Fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid → N-(3-fluoro-4-(2-(4-(methylcarbamoyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide
Reaction equation
[NH2:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[CH:25]=[CH:24][C:19]([C:20]([NH:22][CH3:23])=[O:21])=[CH:18][CH:17]=4)[S:15][C:8]=23)=[C:4]([F:28])[CH:3]=1.[F:29][C:30]1[CH:35]=[CH:34][C:33]([N:36]2[C:41](=[O:42])[C:40]([C:43](O)=[O:44])=[CH:39][CH:38]=[N:37]2)=[CH:32][CH:31]=1>>[F:28][C:4]1[CH:3]=[C:2]([NH:1][C:43]([C:40]2[C:41](=[O:42])[N:36]([C:33]3[CH:34]=[CH:35][C:30]([F:29])=[CH:31][CH:32]=3)[N:37]=[CH:38][CH:39]=2)=[O:44])[CH:27]=[CH:26][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[CH:25]=[CH:24][C:19]([C:20](=[O:21])[NH:22][CH3:23])=[CH:18][CH:17]=3)[S:15][C:8]=12Participants
3
Reactant 2
Product 1
Procedure
Prepared from 4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-N-methylbenzamide (Example 95, Step A) and 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (Example 104, Step C) according to the procedure of Example 89. The crude was purified by silica gel flash column chromatography (3% MeOH in CH2Cl2) to afford 12.5 mg (40%) of the desired product. LRMS (APCI pos) m/e 610.2 (M+1). 1H-NMR (400 MHz, CDCl3/CD3OD) δ 8.46 (d, 1H), 8.41 (d, 1H), 8.33 (d, 1H), 8.01 (dd, 1H), 7.94 (m, 2H), 7.87 (m, 3H), 7.65 (m, 2H), 7.47 (m, 1H), 7.37 (t, 1H), 7.28 (t, 2H), 6.63 (d, 1H), 2.98 (s, 3H); 19F NMR (376 MHz, CDCl3/CD3OD) δ −112.8, −127.6.
Workup
- customThe crude was purified by silica gel flash column chromatography (3% MeOH in CH2Cl2)
Sources & evidence
- ORD record
- ord-af3b6c879f77477fab39c1f6e2c39279
- Source dataset
- uspto-grants-2011_08
- Patent number
- US08003662B2
Reaction notes
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