Water → HCID 57964981, compound

HRID 1931730Notes

Reaction equation

HRID 1931730 reaction equation
Cl[C:2]([O:4][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:3].[CH3:11][C:12]1[C:17]([O:18][C:19]2[N:24]=[CH:23][N:22]=[C:21]3[N:25]([CH:28]4[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)[N:26]=[CH:27][C:20]=23)=[CH:16][CH:15]=[CH:14][N:13]=1.C(N(C(C)C)CC)(C)C.O>ClCCl.CN(C)C1C=CN=CC=1>[CH:5]1([O:4][C:2]([N:31]2[CH2:30][CH2:29][CH:28]([N:25]3[C:21]4=[N:22][CH:23]=[N:24][C:19]([O:18][C:17]5[C:12]([CH3:11])=[N:13][CH:14]=[CH:15][CH:16]=5)=[C:20]4[CH:27]=[N:26]3)[CH2:33][CH2:32]2)=[O:3])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 83262Carbonochloridic acid, cyclohexyl esterHCID 57544435HCID 57544435, compound2×

Product 1

HCID 57964981HCID 57964981, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of cyclohexyl chloroformate (Waterstone Technology, LLC, Carmel, Ind., USA; 42 mg, 0.26 mmol) in dichloromethane (150 μL) was added to a cooled (˜0° C.) solution of 4-(2-methyl-pyridin-3-yloxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine (Intermediate 28; 52 mg, 0.17 mmol), diisopropylethylamine (77 μL, 0.80 mmol) and 4-dimethylaminopyridine (1 mg) in anhydrous dichloromethane (2 mL) over 30 sec. The mixture was stirred at 0° C. for 5 min, then warmed to room temperature and stirred for 1 h. Water (5 mL) was added. The layers were separated and the organic layer was washed with brine, dried (sodium sulfate), filtered, evaporated, and purified on an Isco 4 g column eluting with 0-4% methanol/dichloromethane. Fractions containing the product were pooled, concentrated and lyophilized to give 4-[4-(2-methyl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclohexyl ester (9.6 mg, 13%). Mass spectrum (ES) MH+=437.

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred for 1 h
  3. customThe layers were separated
  4. washthe organic layer was washed with brine
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. customevaporated
  8. custompurified on an Isco 4 g column
  9. washeluting with 0-4% methanol/dichloromethane
  10. additionFractions containing the product
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-03f02044b0f94126b3080beb56867891
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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