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

Participants

Reaction Steps

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.

Provenance & Evidence