Diisopropylethylamine → 4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-1-[(2S)-2-hydroxypropanoyl]piperidine-4-carboxamide

HRID 1867727Notes

Reaction equation

HRID 1867727 reaction equation
CCN(C(C)C)C(C)C.[C:10]([OH:15])(=O)[C@H:11]([CH3:13])[OH:12].Cl.[Cl:17][C:18]1[C:19]([F:49])=[C:20]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([O:47][CH3:48])=[C:32]([CH2:35][N:36]([CH3:46])[C:37]4([C:43]([NH2:45])=[O:44])[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]4)[CH:33]=3)[N:28]=[CH:27][N:26]=2)[CH:21]=[CH:22][CH:23]=1>CN(C)C=O>[Cl:17][C:18]1[C:19]([F:49])=[C:20]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([O:47][CH3:48])=[C:32]([CH2:35][N:36]([CH3:46])[C:37]4([C:43]([NH2:45])=[O:44])[CH2:42][CH2:41][N:40]([C:10](=[O:15])[C@@H:11]([OH:12])[CH3:13])[CH2:39][CH2:38]4)[CH:33]=3)[N:28]=[CH:27][N:26]=2)[CH:21]=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 107689L-Lactic AcidHCID 690487244-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-carboxamide hydrochloride

Product 1

HCID 579798324-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-1-[(2S)-2-hydroxypropanoyl]piperidine-4-carboxamideYield 43.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.120 g, 0.92 mmol) and L-lactic acid (0.083 g, 0.92 mmol) were added to a stirred solution of 4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-carboxamide hydrochloride (0.10 g, 0.184 mmol) in dimethylformamide at room temperature. O-(1H-Benzotriazol-1-yl)-N,N,N′N′-tetramethyluronium tetrafluoroborate (0.295 g, 0.92 mmol) was added and the reaction mixture was stirred for 30 minutes, concentrated and purified by preparative LCMS (standard acidic system) to give the title product (0.044 g, 43.4%) as a white solid; 1H NMR Spectrum: (DMSO-d6) 1.29 (d, 3H), 1.91 (m, 2H), 2.06 (m, 2H), 2.20 (m, 3H), 3.34 (m, 4H), 3.65 (s, 2H), 3.94 (s, 3H), 4.45 (m, 1H), 4.83 (m, 1H), 7.19 (s, 1H), 7.29 (m, 3H), 7.49-7.57 (m, 2H), 8.34 (s, 1H), 8.42 (s, 1H), 9.73 (s, 1H); Mass Spectrum: (M+H)+ 545.

Workup

  1. concentrationconcentrated
  2. custompurified by preparative LCMS (standard acidic system)

Sources & evidence

ORD record
ord-d9df8cf4eb344b0c8e0e30a203054ca1
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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