1-Bromo-2-methylpropane → HCID 178448815, compound

HRID 1403135Notes

Reaction equation

HRID 1403135 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:41])[NH:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([NH:16][C:17]2[CH:22]=[C:21]([N:23]3[C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[N:25]=[C:24]3[CH:32]([F:34])[F:33])[N:20]=[C:19]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[N:18]=2)[CH2:12][CH2:11]1)([CH3:6])([CH3:5])[CH3:4].Br[CH2:43][CH:44]([CH3:46])[CH3:45]>CN(C)C=O>[C:3]([O:7][C:8](=[O:41])[NH:9][C@H:10]1[CH2:11][CH2:12][C@H:13]([N:16]([C:17]2[CH:22]=[C:21]([N:23]3[C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[N:25]=[C:24]3[CH:32]([F:33])[F:34])[N:20]=[C:19]([N:35]3[CH2:36][CH2:37][O:38][CH2:39][CH2:40]3)[N:18]=2)[CH2:43][CH:44]([CH3:46])[CH3:45])[CH2:14][CH2:15]1)([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 65551-Bromo-2-methylpropaneHCID 24758Sodium hydrideHCID 178454002HCID 178454002, compound

Product 1

HCID 178448815HCID 178448815, compoundYield 14.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

60% Sodium hydride (110 mg) was suspended in N,N-dimethylformamide (20 mL), and tert-butyl[trans-4-({6-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-2-(morpholin-4-yl)pyrimidin-4-yl}amino)cyclohexyl]carbamate (1 g) was added thereto at 0° C., followed by stirring at room temperature for 30 minutes. To the reaction mixture was added a 1-bromo-2-methylpropan (807 mg), followed by stirring at room temperature for 12 hours. After the completion of the reaction, to the reaction solution was added ice water, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified using silica gel chromatography to obtain tert-butyl{trans-4-[{6-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-2-(morpholin-4-yl)pyrimidin-4-yl}(isobutyl)amino]cyclohexyl}carbamate (163 mg).

Workup

  1. customat 0° C.
  2. stirringby stirring at room temperature for 12 hours
  3. customAfter the completion of the reaction
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was purified

Sources & evidence

ORD record
ord-db87d5d832c449d2b511f7c3652948f6
Source dataset
uspto-grants-2014_12
Patent number
US08912180B2

Reaction notes

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