Trifluoroacetic acid methylene chloride → 4-[4-(2-Fluoro-4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid

HRID 1931725Notes

Reaction equation

HRID 1931725 reaction equation
C([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22]([O:23][C:24]4[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][C:25]=4[F:34])=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.FC(F)(F)C(O)=O.ClCCl>CO.ClCCl>[F:34][C:25]1[CH:26]=[C:27]([S:30]([CH3:33])(=[O:32])=[O:31])[CH:28]=[CH:29][C:24]=1[O:23][C:22]1[N:21]=[CH:20][N:19]=[C:18]2[N:14]([CH:11]3[CH2:12][CH2:13][N:8]([C:6]([OH:7])=[O:5])[CH2:9][CH2:10]3)[N:15]=[CH:16][C:17]=12

Participants

4

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 44514402HCID 44514402, compound

Product 1

HCID 669155484-[4-(2-Fluoro-4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acidYield 103.8%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

A mixture of 4-[4-(2-fluoro-4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (Example 60; 520 mg, 1.06 mmol) and 20% trifluoroacetic acid/dichloromethane (12 mL) was stirred at room temperature until tlc (6% methanol/dichloromethane) indicated that the starting material had completely reacted. The solvent was evaporated, ether (5 mL) was added, and the mixture was evaporated to give a white semi-solid which was held under vacuum, then triturated with ether, and held under high vacuum to give 4-[4-(2-fluoro-4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid (479 mg, 90%) as a white powder. A mixture of 40 mg of this powder (0.08 mmol) and diisopropylethylamine (42 μL) in anhydrous dichloromethane (1 mL) was cooled to 0° C. and a solution of cyclopentyl chloroformate (Waterstone Technology, LLC, Carmel, Ind., USA; 18 mg, 0.12 mmol) in dichloromethane (250 μL) was added dropwise. The mixture was stirred at room temperature for 30 min. Water (3 mL) was added. The layers were separated and the organic layer was washed with brine, dried (sodium sulfate), filtered, evaporated, co-evaporated with ether and purified on a Silicycle 4 g column eluting with 0-10% methanol/dichloromethane to give 4-[4-(2-fluoro-4-methanesulfonyl-phenoxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester (27 mg, 68%) as a white solid.

Workup

  1. customhad completely reacted
  2. customThe solvent was evaporated
  3. additionether (5 mL) was added
  4. customthe mixture was evaporated
  5. customto give a white semi-solid which
  6. customtriturated with ether

Sources & evidence

ORD record
ord-ef6b55f3116946388923401161f29daf
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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