Ethyl (S)-2-(trifluoromethylsulfonyloxy)propionate → N-({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)-N-[(1S)-2-methoxy-1-methylethyl]-D-alanine

HRID 1867710Notes

Reaction equation

HRID 1867710 reaction equation
[Cl:1][C:2]1[C:3]([F:28])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:26][CH3:27])=[C:16]([CH2:19][NH:20][C@@H:21]([CH3:25])[CH2:22][O:23][CH3:24])[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CC[O:31][C:32]([C@@H:34](OS(C(F)(F)F)(=O)=O)[CH3:35])=[O:33]>>[Cl:1][C:2]1[C:3]([F:28])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:26][CH3:27])=[C:16]([CH2:19][N:20]([C@@H:21]([CH3:25])[CH2:22][O:23][CH3:24])[C@@H:34]([C:32]([OH:33])=[O:31])[CH3:35])[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 11207429Ethyl (S)-2-(trifluoromethylsulfonyloxy)propionateHCID 69048997N-(3-chloro-2-fluorophenyl)-7-methoxy-6-({[(1S)-2-methoxy-1-methylethyl]amino}methyl)quinazolin-4-amine

Product 1

HCID 57979849N-({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)-N-[(1S)-2-methoxy-1-methylethyl]-D-alanine

Procedure

N-(3-Chloro-2-fluorophenyl)-7-methoxy-6-({[(1S)-2-methoxy-1-methylethyl]amino}methyl)quinazolin-4-amine was coupled with ethyl O-trifluoromethanesulfonyl-L-lactate and hydrolysed using analogous methods to those described for the equivalent steps in Example 46 to give N-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)-N-[(1S)-2-methoxy-1-methylethyl]-D-alanine; 1H NMR Spectrum: (DMSO-d6) 1.08 (d, 3H); 1.32 (d, 3H); 3.04 (m, 1H); 3.14 (s, 3H); 3.22 (dd, 1H); 3.43 (dd, 1H); 3.69 (q, 1H); 3.96 (m, 4H); 4.05 (d, 1H); 7.19 (s, 1H); 7.29 (t, 1H); 7.49 (t, 1H); 7.60 (t, 1H); 8.43 (m, 2H); 9.64 (brs, 1H); 12.01 (brs, 1H); Mass Spectrum: (M+H)+ 477.

Sources & evidence

ORD record
ord-c22d406792c842d8a43114b376cf4fff
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

Loading…