3-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline → 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-isopropyl-1-(pyridin-3-yl)-1H-pyrazol-5-yl)urea
Reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].[CH:23]([C:26]1[CH:30]=[C:29]([NH:31][C:32](=O)[O:33]C2C=CC=CC=2)[N:28]([C:41]2[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=2)[N:27]=1)([CH3:25])[CH3:24]>C1COCC1.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:17]=[C:18]([NH:19][C:32]([NH:31][C:29]2[N:28]([C:41]3[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=3)[N:27]=[C:26]([CH:23]([CH3:25])[CH3:24])[CH:30]=2)=[O:33])[CH:20]=[CH:21][CH:22]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Procedure
Using the procedure described in Example 306B, to a solution of 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline (91 mg, 0.3 mmol), prepared as described in Example 113A, in THF (2 ml) was added DMAP (20 mg, 0.16 mmol) and phenyl 3-isopropyl-1-(pyridin-3-yl)-1H-pyrazol-5-ylcarbamate (110 mg, 0.34 mmol), described in the previous step. The crude was purified by silica gel chromatography (DCM/MeOH 2-10%) to afford 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-isopropyl-1-(pyridin-3-yl)-1H-pyrazol-5-yl)urea (91 mg, 58%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 1.22 (d, J=7 Hz, 6H), 2.89 (m, 1H), 3.99 (s, 6H), 6.35 (s, 1H), 6.92 (d, J=7.8 Hz, 1H), 7.19 (d, J=7.8 Hz, 1H), 7.34-7.39 (m, 2H), 7.52-7.55 (m, 3H), 7.97 (d, J=7.2 Hz, 1H), 8.55 (s, 1H), 8.58-8.60 (m, 2H), 8.77 (d, J=2.4 Hz, 1H), 9.19 (s, 1H); LC-MS (ESI) m/z 526 (M+H)+.
Workup
- customprepared
- customThe crude was purified by silica gel chromatography (DCM/MeOH 2-10%)
Sources & evidence
- ORD record
- ord-8471a8a99796456caed50049e6d44565
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08969587B2
Reaction notes
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