Water → 4-[4-(4-Ethoxy-2-fluorophenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester

HRID 1931722Notes

Reaction equation

HRID 1931722 reaction equation
Cl[C:2]([O:4][CH:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:3].FC(F)(F)C(O)=O.[CH2:17]([O:19][C:20]1[CH:41]=[CH:40][C:23]([O:24][C:25]2[N:30]=[CH:29][N:28]=[C:27]3[N:31]([CH:34]4[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]4)[N:32]=[CH:33][C:26]=23)=[C:22]([F:42])[CH:21]=1)[CH3:18].C(N(C(C)C)CC)(C)C.O>ClCCl>[CH:5]1([O:4][C:2]([N:37]2[CH2:38][CH2:39][CH:34]([N:31]3[C:27]4=[N:28][CH:29]=[N:30][C:25]([O:24][C:23]5[CH:40]=[CH:41][C:20]([O:19][CH2:17][CH3:18])=[CH:21][C:22]=5[F:42])=[C:26]4[CH:33]=[N:32]3)[CH2:35][CH2:36]2)=[O:3])[CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 2735892Cyclopentyl chloroformateHCID 669153124-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2×

Product 1

HCID 579649964-[4-(4-Ethoxy-2-fluorophenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl esterYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Cyclopentyl chloroformate (12 mg, 0.078 mmol) was added to a mixture of 4-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 29; 28 mg, 0.078 mmol), diisopropylethylamine (30 mg, 0.235 mmol) in dichloromethane (2 mL). The reaction was stirred at room temperature overnight. Water was added to quench the reaction and the aqueous layer was extracted three times with dichloromethane. The combined organic layers were dried (sodium sulfate), filtered, evaporated and purified by flash chromatography on silica gel, eluting with 4% methanol/dichloromethane to give 4-[4-(4-ethoxy-2-fluorophenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester (36 mg, 99%) as a white solid. Mass spectrum MH+=470.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe aqueous layer was extracted three times with dichloromethane
  4. dry with materialThe combined organic layers were dried (sodium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by flash chromatography on silica gel
  8. washeluting with 4% methanol/dichloromethane

Sources & evidence

ORD record
ord-5cc5e7673e4e4a61b387c52055167a29
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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