Water → HCID 25122893, compound

HRID 1931709Notes

Reaction equation

HRID 1931709 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][CH2:36][CH2:37][CH3:38])=O.C(N([CH2:44][CH3:45])CC)C.O.F[C:48](F)(F)C(O)=O>ClCCl>[CH2:38]([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:37]1[CH:45]=[CH:44][CH:48]=[CH:35][CH:36]=1

Participants

7

Reactant 5

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 61140Butyl chloroformateHCID 44622155HCID 44622155, compound

Product 1

HCID 25122893HCID 25122893, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 under vacuum. Dichloromethane (4 mL) was added, followed successively by n-butyl chloroformate (24 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 (24 mg) as a waxy solid. 1H NMR showed that this material contained almost one mole equivalent of triethylamine hydrochloride. HRMS Calcd. For C21H27N6O3 (MH+): 411.2139. Found: 411.2139.

Workup

  1. customthe solvents were evaporated under vacuum
  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-c1cc3856ba964092958dcc89c3bdfde5
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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