Trifluoroacetic acid → HCID 58318651, compound

HRID 1027916Notes

Reaction equation

HRID 1027916 reaction equation
C(O)(C(F)(F)F)=O.[NH2:8][C:9]([C@@H:11]1[CH2:16][C@@H:15]([O:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][C:27]=2[O:28][CH3:29])[N:24]=[CH:23][N:22]=[C:21]3[NH:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=2[F:38])[CH2:14][CH2:13][N:12]1C(OC(C)(C)C)=O)=[O:10]>C(Cl)Cl>[Cl:37][C:33]1[C:32]([F:38])=[C:31]([NH:30][C:21]2[C:20]3[C:25](=[CH:26][C:27]([O:28][CH3:29])=[C:18]([O:17][C@H:15]4[CH2:14][CH2:13][NH:12][C@H:11]([C:9]([NH2:8])=[O:10])[CH2:16]4)[CH:19]=3)[N:24]=[CH:23][N:22]=2)[CH:36]=[CH:35][CH:34]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58318668HCID 58318668, compound

Product 1

HCID 58318651HCID 58318651, compoundYield 76%

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)-2-(aminocarbonyl)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)piperidine-1-carboxylate (4) (5 g, 9.16 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 and the residue was purified by flash chromatography (silica gel, DCM-NH3/MeOH 5%) to give (2S,4S)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)piperidine-2-carboxamide (5) (3.1 g, 76%) as a white solid: 1H NMR Spectrum: (DMSO d6) 1.72-1.89 (m, 2H), 1.91 (m, 1H), 2.03 (m, 1H), 2.78 (m, 1H), 2.92 (m, 1H), 3.47 (m, 1H), 3.95 (s, 3H), 4.84 (m, 1H), 7.06 (s, 1H), 7.27 (s, 1H), 7.30 (m, 2H), 7.49-7.55 (m, 2H), 7.84 (s, 1H), 8.37 (s, 1H), 9.56 (s, 1H), Mass Spectrum: (M+H)+ 446.1.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customazeotroped twice with toluene
  3. customthe residue was purified by flash chromatography (silica gel, DCM-NH3/MeOH 5%)

Sources & evidence

ORD record
ord-0afb711384cd443da4c7e1b9f893b85a
Source dataset
uspto-grants-2014_05
Patent number
US08735410B2

Reaction notes

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