(2R)-2-(methylamino)propanamide → N2-(1-{4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}ethyl)-N2-methyl-D-alaninamide
Reaction equation
Cl.Cl[CH:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][CH3:16])[N:11]=[CH:10][N:9]=[C:8]2[NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:19]=1[F:25])[CH3:4].[CH3:26][NH:27][C@@H:28]([C:30]([NH2:32])=[O:31])[CH3:29]>>[Cl:24][C:20]1[C:19]([F:25])=[C:18]([NH:17][C:8]2[C:7]3[C:12](=[CH:13][C:14]([O:15][CH3:16])=[C:5]([CH:3]([N:27]([CH3:26])[C@@H:28]([C:30]([NH2:32])=[O:31])[CH3:29])[CH3:4])[CH:6]=3)[N:11]=[CH:10][N:9]=2)[CH:23]=[CH:22][CH:21]=1Participants
3
Procedure
6-(1-Chloroethyl)-N-(3-chloro-2-fluorophenyl)-7-methoxyquinazolin-4-amine hydrochloride (described in Example 91) was coupled with N2-methyl-D-alaninamide using an analogous method to that described for the equivalent step in Example 62 to give N2-(1-{4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}ethyl)-N2-methyl-D-alaninamide as a 1:1 mixture of diastereoisomers; 1H NMR Spectrum: (DMSO d6) 1.03 and 1.08 (both d, 1.5H); 1.38 (d, 3H); 2.06 and 2.22 (both s, 1.5H); 3.13 and 3.51 (both q, 0.5H); 3.97 (s, 3H); 4.31 (m, 1H); 7.07 (s, 1H); 7.22 (m, 1H); 7.23 (m, 1.5H); 7.44 (s, 0.5H); 7.53 (m, 2H); 8.44 (m, 1.5H); 8.60 (s, 0.5H); 9.77 and 9.80 (both s, 0.5H). Mass Spectrum: (M+H)+ 432.
Sources & evidence
- ORD record
- ord-49eb60650c254c52996a590450ac89ab
- Source dataset
- uspto-grants-2009_12
- Patent number
- US07632840B2
Reaction notes
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