Water → HCID 25122893, compound

HRID 1931729Notes

Reaction equation

HRID 1931729 reaction equation
C([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22]([O:23][C:24]4[C:25]([CH3:30])=[N:26][CH:27]=[CH:28][CH:29]=4)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.ClC(O[CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=O.C(N(CC)CC)C.O>FC(F)(F)C(O)=O.ClCCl>[CH2:35]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22]([O:23][C:24]4[C:25]([CH3:30])=[N:26][CH:27]=[CH:28][CH:29]=4)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 44622155HCID 44622155, compound

Product 1

HCID 25122893HCID 25122893, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 4-[4-(2-methyl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (Example 92; 50 mg, 0.12 mmol) in a mixture of trifluoroacetic acid (0.5 mL) and dichloromethane (2 mL) was stirred at room temperature for 30 min, then the solvents were evaporated and the residue held under high vacuum. Dichloromethane (4 mL) was added, followed successively by benzyl chloroformate (26 μL, 0.18 mmol) and triethylamine (110 μL, 0.8 mmol). The mixture was stirred overnight at room temperature. Water was added and the mixture was extracted with three times with dichloromethane. The combined dichloromethane layers were evaporated and the residue was purified by C18 reversed phase HPLC using a gradient of 10-100% acetonitrile/water to give 4-[4-(2-methyl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid benzyl ester (16 mg, 29%) as a white powder. HRMS Calcd. For C24H25N6O3 (MH+): 445.1983. Found: 445.1981.

Workup

  1. customthe solvents were evaporated
  2. additionDichloromethane (4 mL) was added
  3. stirringThe mixture was stirred overnight at room temperature
  4. extractionthe mixture was extracted with three times with dichloromethane
  5. customThe combined dichloromethane layers were evaporated
  6. customthe residue was purified by C18 reversed phase HPLC

Sources & evidence

ORD record
ord-ecaf177c24a24e2a9ef9eadbde16fa6f
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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