(S)-1-(5-tert-butylisoxazol-3-yl)-3-(3-(6-methoxy-7-(pyrrolidin-3-yloxy)quinazolin-4-yloxy)phenyl)urea dihydrochloride → (R)-1-(5-tert-butylisoxazol-3-yl)-3-(3-(6-methoxy-7-(pyrrolidin-3-yloxy)quinazolin-4-yloxy)phenyl)urea dihydrochloride
Reaction equation
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11](=[O:45])[NH:12][C:13]2[CH:14]=[C:15]([CH:42]=[CH:43][CH:44]=2)[O:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:29][C@@H:30]4[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31]4)=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[ClH:46].Cl.C(C1ON=C(NC(NC2C=CC=C(OC3C4C(=CC(O[C@H]5CCNC5)=C(OC)C=4)N=CN=3)C=2)=O)C=1)(C)(C)C>>[ClH:46].[ClH:46].[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:12][C:13]2[CH:44]=[CH:43][CH:42]=[C:15]([O:16][C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:29][C@@H:30]5[CH2:34][CH2:33][NH:32][CH2:31]5)=[C:24]([O:27][CH3:28])[CH:25]=4)[N:20]=[CH:19][N:18]=3)[CH:14]=2)=[O:45])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]Participants
Reactant 2
Product 1
Procedure
Prepared from (R)-tert-butyl 3-(4-(3-(3-(5-tert-butylisoxazol-3-yl)ureido)phenoxy)-6-methoxyquinazolin-7-yloxy)pyrrolidine-1-carboxylate from the previous step (109 mg, 0.176 mmol) according to the procedure described for (S)-1-(5-tert-butylisoxazol-3-yl)-3-(3-(6-methoxy-7-(pyrrolidin-3-yloxy)quinazolin-4-yloxy)phenyl)urea dihydrochloride in Example 96B to afford (R)-1-(5-tert-butylisoxazol-3-yl)-3-(3-(6-methoxy-7-(pyrrolidin-3-yloxy)quinazolin-4-yloxy)phenyl)urea dihydrochloride as a colorless solid (42 mg, 40%). 1H NMR (300 MHz, CDCl3) δ 9.30 (brs, 1H), 8.61 (brs, 1H), 7.65 (s, 1H), 7.52 (s, 1H), 7.20-7.40 (m, 4H), 6.99 (m, 1H), 6.02 (s, 1H), 5.05 (m, 1H), 4.01 (s, 3H), 3.10-3.40 (m, 2H), 3.00 (m, 1H), 2.00-2.40 (m, 4H), 1.40 (s, 9H); LC-MS (ESI) m/z 519 (M+H)+.
Sources & evidence
- ORD record
- ord-960729e4289c45c8bfe11c9a0e6ed5ad
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08969587B2
Reaction notes
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