Diisopropylethylamine → 4-[4-(2-Cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester

HRID 1931723Notes

Reaction equation

HRID 1931723 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.[NH:17]1[CH2:22][CH2:21][CH:20]([N:23]2[C:27]3=[N:28][CH:29]=[N:30][C:31]([O:32][C:33]4[CH:40]=[CH:39][CH:38]=[CH:37][C:34]=4[C:35]#[N:36])=[C:26]3[CH:25]=[N:24]2)[CH2:19][CH2:18]1.C(OC(N1CCC(N2C3=NC=NC(OC4C=CC=CC=4C#N)=C3C=N2)CC1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(OC1C=CC(OC2N=CN=C3N(C4CCNCC4)N=CC=23)=C(F)C=1)C.C(N(C(C)C)CC)(C)C>ClCCl.O>[CH:5]1([O:4][C:2]([N:17]2[CH2:22][CH2:21][CH:20]([N:23]3[C:27]4=[N:28][CH:29]=[N:30][C:31]([O:32][C:33]5[CH:40]=[CH:39][CH:38]=[CH:37][C:34]=5[C:35]#[N:36])=[C:26]4[CH:25]=[N:24]3)[CH2:19][CH2:18]2)=[O:3])[CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 2735892Cyclopentyl chloroformateHCID 445144014-[4-(2-Cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl esterHCID 669153124-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate saltHCID 669154562-(1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine-4-yloxy)-benzonitrile trifluoroacetate salt

Product 1

HCID 579649284-[4-(2-Cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl esterYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Cyclopentyl chloroformate (51 mg, 0.344 mmol) was added to a mixture of 2-(1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine-4-yloxy)-benzonitrile trifluoroacetate salt (which was prepared from 4-[4-(2-cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester [Example 45] following the procedure described for the preparation of Intermediate 29; 150 mg, 0.344 mmol), diisopropylethylamine (133 mg, 1.03 mmol) in dichloromethane (6 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-(2-cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester (107 mg, 72%) as a white solid. Mass spectrum MH+=433.

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-35bf9104722d4da7b711e280f6a232c8
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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