Water → Cyclopentyl-{4-[4-(4-ethoxy-2-fluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidin-1-yl}-methanone

HRID 1931750Notes

Reaction equation

HRID 1931750 reaction equation
[CH:1]1([C:6](Cl)=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O.[CH2:16]([O:18][C:19]1[CH:40]=[CH:39][C:22]([O:23][C:24]2[N:29]=[CH:28][N:27]=[C:26]3[N:30]([CH:33]4[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]4)[N:31]=[CH:32][C:25]=23)=[C:21]([F:41])[CH:20]=1)[CH3:17].C(N(C(C)C)CC)(C)C.O>ClCCl>[CH:1]1([C:6]([N:36]2[CH2:37][CH2:38][CH:33]([N:30]3[C:26]4=[N:27][CH:28]=[N:29][C:24]([O:23][C:22]5[CH:39]=[CH:40][C:19]([O:18][CH2:16][CH3:17])=[CH:20][C:21]=5[F:41])=[C:25]4[CH:32]=[N:31]3)[CH2:34][CH2:35]2)=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 78284Cyclopentanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 669153124-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2×

Product 1

HCID 57964888Cyclopentyl-{4-[4-(4-ethoxy-2-fluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidin-1-yl}-methanoneYield 87.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Cyclopentanecarbonyl chloride (10 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), and diisopropylethylamine (30 mg, 0.235 mmol) in dichloromethane (2 mL). The reaction mixture 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 cyclopentyl-{4-[4-(4-ethoxy-2-fluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidin-1-yl}-methanone (31 mg, 87%) as a white solid. Mass spectrum MH+=454.

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-7c4920e6a29949649a86f2cd8161fab8
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

Loading…