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

HRID 1931627Notes

Reaction equation

HRID 1931627 reaction equation
Cl[C:2]([O:4][CH:5]([CH3:7])[CH3:6])=[O:3].FC(F)(F)C(O)=O.[CH2:15]([O:17][C:18]1[CH:39]=[CH:38][C:21]([O:22][C:23]2[N:28]=[CH:27][N:26]=[C:25]3[N:29]([CH:32]4[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]4)[N:30]=[CH:31][C:24]=23)=[C:20]([F:40])[CH:19]=1)[CH3:16].C(N(C(C)C)CC)(C)C.O>ClCCl>[CH:5]([O:4][C:2]([N:35]1[CH2:36][CH2:37][CH:32]([N:29]2[C:25]3=[N:26][CH:27]=[N:28][C:23]([O:22][C:21]4[CH:38]=[CH:39][C:18]([O:17][CH2:15][CH3:16])=[CH:19][C:20]=4[F:40])=[C:24]3[CH:31]=[N:30]2)[CH2:33][CH2:34]1)=[O:3])([CH3:7])[CH3:6]

Participants

6

Reactant 4

HCID 962WaterHCID 7917Isopropyl chloroformateHCID 81531DiisopropylethylamineHCID 669153124-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2×

Product 1

HCID 445141074-[4-(4-Ethoxy-2-fluoro-phenoxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl esterYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Isopropyl chloroformate (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA; 1 M in toluene; 0.079 ml, 0.079 mol) 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 4-[4-(4-ethoxy-2-fluoro-phenoxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester (27 mg, 80%) as a white solid. Mass spectrum MH+=444.

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-ccc304c697684e2285c124d684373d75
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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