Trifluoroacetic acid → HCID 11612313, compound

HRID 1027923Notes

Reaction equation

HRID 1027923 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 67240730HCID 67240730, compound

Product 1

HCID 11612313HCID 11612313, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (25 ml) was added over a period of 5 minutes to a stirred solution of tert-butyl (2R,4R)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-2-[(methylamino)carbonyl]piperidine-1-carboxylate (5.94 g, 10.63 mmol) in DCM (25 ml) at 0° C., was added. 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 (2R,4R)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-N-methylpiperidine-2-carboxamide (3.6 g, 74%) as a white solid: 1H NMR Spectrum: (DMSO d6) 1.60-2.03 (m, 4H), 2.50-2.58 (m, 1H), 2.59 (d, 3H), 2.78 (m, 1H), 3.53 (m, 1H), 3.84 (s, 1H), 3.96 (s, 3H), 4.84 (m, 1H), 7.27 (s, 1H), 7.35 (t, 1H), 7.47-7.60 (m, 2H), 7.85 (m, 2H), 8.38 (s, 1H), 9.56 (s, 1H); Mass Spectrum: (M+H)+ 460.1.

Workup

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

Sources & evidence

ORD record
ord-84f6c76f6bbd412191434b1a9207d633
Source dataset
uspto-grants-2014_05
Patent number
US08735410B2

Reaction notes

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