L-2,4-Diaminobutyric acid → (3S)-3-[(1-{4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}ethyl)amino]pyrrolidin-2-one

HRID 1867763

Reaction equation

HRID 1867763 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].[NH2:26][C@H:27]1[CH2:31][CH2:30][NH:29][C:28]1=[O:32].N[C@@H](CCN)C(O)=O>>[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]([NH:26][C@H:27]4[CH2:31][CH2:30][NH:29][C:28]4=[O:32])[CH3:4])[CH:6]=3)[N:11]=[CH:10][N:9]=2)[CH:23]=[CH:22][CH:21]=1

Participants

4

Reactant 3

HCID 134490L-2,4-Diaminobutyric acidHCID 12430456(3S)-3-aminopyrrolidin-2-oneHCID 690475966-(1-chloroethyl)-N-(3-chloro-2-fluorophenyl)-7-methoxyquinazolin-4-amine hydrochloride

Product 1

HCID 57979850(3S)-3-[(1-{4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}ethyl)amino]pyrrolidin-2-one

Procedure

6-(1-Chloroethyl)-N-(3-chloro-2-fluorophenyl)-7-methoxyquinazolin-4-amine hydrochloride (Described in Example 91) was coupled with (3S)-3-aminopyrrolidin-2-one (prepared from (2S)-2,4-diaminobutanoic acid according to the method in Synthesis 1978, 614) using an analogous method to that described for the equivalent step in Example 62 to give (3S)-3-[(1-{4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}ethyl)amino]pyrrolidin-2-one as a 1:1 mixture of diastereoisomers; 1H NMR Spectrum: (DMSO d6) 1.42 and 1.46 (both d, 1.5H); 1.71 and 1.81 (both m, 0.5H); 2.09 and 2.31 (both m, 0.5H); 3.00 (t, 0.5H); 3.11 (m, 1.5H); 3.23 (t, 1H); 4.03 (s, 3H); 4.27 and 4.52 (both m, 0.5H); 7.25 and 7.27 (both s, 0.5H); 7.34 (m, 1H); 7.53 (m, 1H); 7.61 (m, 1H); 7.74 and 7.77 (both s, 0.5H); 8.49 (m, 2H); 9.79 and 9.88 (both s, 0.5H); Mass Spectrum: (M+H)+ 430.

Sources & evidence

ORD record
ord-0b83babf2b834a0498a01752ba2015f0
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Linked notes

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