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

HRID 1931628Notes

Reaction equation

HRID 1931628 reaction equation
ClC(OC(C)C)=O.FC(F)(F)C(O)=O.N1CCC(N2C3=NC=NC(OC4C=CC=CC=4C#N)=C3C=N2)CC1.[C:39]([O:43][C:44]([N:46]1[CH2:51][CH2:50][CH:49]([N:52]2[C:56]3=[N:57][CH:58]=[N:59][C:60]([O:61][C:62]4[CH:67]=[CH:66][CH:65]=[CH:64][C:63]=4[C:68]#[N:69])=[C:55]3[CH:54]=[N:53]2)[CH2:48][CH2:47]1)=[O:45])(C)([CH3:41])[CH3:40].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:39]([O:43][C:44]([N:46]1[CH2:47][CH2:48][CH:49]([N:52]2[C:56]3=[N:57][CH:58]=[N:59][C:60]([O:61][C:62]4[CH:67]=[CH:66][CH:65]=[CH:64][C:63]=4[C:68]#[N:69])=[C:55]3[CH:54]=[N:53]2)[CH2:50][CH2:51]1)=[O:45])([CH3:41])[CH3:40]

Participants

8

Reactant 5

HCID 7917Isopropyl chloroformateHCID 81531DiisopropylethylamineHCID 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 445141084-[4-(2-Cyano-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl esterYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Isopropyl chloroformate (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 1M in toluene; 0.34 mL, 0.34 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 isopropyl ester (98 mg, 70%) as a white solid. Mass spectrum MH+=407.

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-b96fc3b0c07f45f791fdfa71ecbcb222
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

Loading…