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

HRID 897970Notes

Reaction equation

HRID 897970 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-1376a586c1a544419a80c056c308f9f6
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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