2-Fluoro-4-(trifluoromethyl)benzoyl chloride → HCID 22346659, compound

HRID 2056147Notes

Reaction equation

HRID 2056147 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12](Cl)=[O:13].[NH2:15][C:16]1[N:21]=[CH:20][N:19]=[C:18]2[N:22]([CH:34]3[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]3)[N:23]=[C:24]([C:25]3[CH:30]=[CH:29][C:28]([NH2:31])=[C:27]([O:32][CH3:33])[CH:26]=3)[C:17]=12>ClCCl.N1C=CC=CC=1>[NH2:15][C:16]1[N:21]=[CH:20][N:19]=[C:18]2[N:22]([CH:34]3[CH2:35][CH2:36][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:38][CH2:39]3)[N:23]=[C:24]([C:25]3[CH:30]=[CH:29][C:28]([NH:31][C:12](=[O:13])[C:3]4[CH:4]=[CH:5][C:6]([C:8]([F:11])([F:10])[F:9])=[CH:7][C:2]=4[F:1])=[C:27]([O:32][CH3:33])[CH:26]=3)[C:17]=12

Participants

5

Reactant 2

HCID 1455802-Fluoro-4-(trifluoromethyl)benzoyl chloride2×HCID 22347369HCID 22347369, compound

Product 1

HCID 22346659HCID 22346659, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

2-Fluoro-4-(trifluoromethyl)-1-benzenecarbonyl chloride (3.05 mL, 20.2 mmol) in dichloromethane (25 mL) was added to a solution of tert-butyl 4-[4-amino-3-(4-amino-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate (8.77 g, 20.0 mmol) in pyridine (50 mL) at 0° C. After 5 minutes, the ice water bath was removed and the reaction mixture stirred at room temperature for 1 hours. 2-Fluoro-4-(trifluoromethyl)-1-benzenecarbonyl chloride (0.5 mL, 3.31 mmol) was added and the reaction mixture was stirred for addition 30 minutes. The solvent was evaporated and the residue was dissolved in dichloromethane. The organic layer was washed with water, brine then dried over MgSO4. The solvent was evaporated and the residue was purified by flash column chromatography using ethyl acetate/dichloromethane (80:20 to 100:0) as mobile phase to give tert-Butyl 4-[4-amino-3-(4-[2-fluoro-4-(trifluoromethyl)benzoyl]amino-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate (11.2 g, 89%). 1H NMR (CDCl3-d) δ 1.48 (s, 9H), 2.04 (m, 2H), 2.30 (m, 2H), 2.98 (m, 2H), 4.05 (s, 3H), 4.32 (m, 2H), 4.95 (m, 1H), 5.89 (bs, 2H), 7.33 (m, 2H), 7.51 (d, J=11.62 Hz, 1H), 7.61 (d, J=8.21 Hz, 1H), 8.36 (m, 2H), 8.72 (d, J=8.18 Hz, 1H), 9.32 (d, J=14.39 Hz, 1H).

Workup

  1. customthe ice water bath was removed
  2. stirringthe reaction mixture was stirred for addition 30 minutes
  3. customThe solvent was evaporated
  4. dissolutionthe residue was dissolved in dichloromethane
  5. washThe organic layer was washed with water, brine
  6. dry with materialthen dried over MgSO4
  7. customThe solvent was evaporated
  8. customthe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-c809b26194df483cb289fd6f457ed580
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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