1-(4-Fluorophenyl)-2-oxo-3-pyrrolidinecarboxylic acid → N-(3-fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxopyrrolidine-3-carboxamide
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:28])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]#[C:19][CH2:20][N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)[S:17][C:10]=12.[F:29][C:30]1[CH:35]=[CH:34][C:33]([N:36]2[CH2:40][CH2:39][CH:38]([C:41](O)=[O:42])[C:37]2=[O:44])=[CH:32][CH:31]=1>>[F:1][C:2]1[CH:3]=[C:4]([NH:28][C:41]([CH:38]2[CH2:39][CH2:40][N:36]([C:33]3[CH:34]=[CH:35][C:30]([F:29])=[CH:31][CH:32]=3)[C:37]2=[O:44])=[O:42])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]#[C:19][CH2:20][N:21]3[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]3)[S:17][C:10]=12Participants
3
Reactant 2
Product 1
Procedure
The title compound was prepared from 3-fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)aniline (Example 17, Step B) and 1-(4-fluorophenyl)-2-oxopyrrolidine-3-carboxylic acid according to the procedure described for Example 89. The crude was purified by silica gel flash column chromatography (5% MeOH in CH2Cl2) to afford 4.7 mg (31%) of the desired product. 1H NMR (400 MHz, CD3OD) δ 8.49 (d, 1H), 7.89 (dd, 1H), 7.63 (m, 2H), 7.60 (s, 1H), 7.45 (m, 1H), 7.37 (t, 1H), 7.14 (t, 2H), 6.69 (d, 1H), 3.97 (m, 2H), 3.68 (s, 2H), 2.75 (m, 4H), 2.58 (m, 3H), 2.47 (m, 3H), 2.30 (s, 3H); 19F NMR (376 MHz, CD3OD) δ −119.2, −129.9. LRMS (ESI pos) m/e 602.3 (M+1).
Workup
- customThe crude was purified by silica gel flash column chromatography (5% MeOH in CH2Cl2)
Sources & evidence
- ORD record
- ord-1a24b9b0d2de4509ac5253010e32438c
- Source dataset
- uspto-grants-2011_08
- Patent number
- US08003662B2
Reaction notes
Loading…