Trifluoroacetic acid → (2S,4S)-4-[[4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxy-6-quinazolinyl]oxy]-N-methyl-2-piperidinecarboxamide

HRID 1027919Notes

Reaction equation

HRID 1027919 reaction equation
C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[C:10]([F:46])=[C:11]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:44][CH3:45])=[C:23]([O:26][C@H:27]4[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[C@H:29]([C:40]([NH:42][CH3:43])=[O:41])[CH2:28]4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1>C(Cl)Cl>[Cl:8][C:9]1[C:10]([F:46])=[C:11]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:44][CH3:45])=[C:23]([O:26][C@H:27]4[CH2:32][CH2:31][NH:30][C@H:29]([C:40]([NH:42][CH3:43])=[O:41])[CH2:28]4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67238793HCID 67238793, compound

Product 1

HCID 67238726(2S,4S)-4-[[4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxy-6-quinazolinyl]oxy]-N-methyl-2-piperidinecarboxamideYield 89.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (15 ml) was added over a period of 5 minutes to a stirred solution of tert-butyl (2S,4S)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-2-[(methylamino)carbonyl]piperidine-1-carboxylate (4.1 g, 7.31 mmol) in DCM (15 ml) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour after which time, the reaction was complete. The reaction mixture was concentrated to dryness, azeotroped twice with toluene to give (2S,4S)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-N-methylpiperidine-2-carboxamide (3.0 g, 89%) the crude residue was used without further purification; Mass Spectrum: (M+H)+ 460.1.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customazeotroped twice with toluene

Sources & evidence

ORD record
ord-75329f52f3034576b39b89933849259a
Source dataset
uspto-grants-2014_05
Patent number
US08735410B2

Reaction notes

Loading…