Potassium Carbonate → HCID 178432914, compound

HRID 245711Notes

Reaction equation

HRID 245711 reaction equation
C(OC(N[C@H]1CC[C@H](C(O)=O)CC1)=O)C1C=CC=CC=1.[Br:21][C:22]1[N:23]=[C:24]([C@H:32]2[CH2:37][CH2:36][C@H:35]([NH2:38])[CH2:34][CH2:33]2)[N:25]2[CH:30]=[CH:29][N:28]=[C:27]([CH3:31])[C:26]=12.C(=O)([O-])[O-].[K+].[K+].Br[CH2:46][CH:47]([F:49])[F:48]>CN(C)C=O>[Br:21][C:22]1[N:23]=[C:24]([C@H:32]2[CH2:37][CH2:36][C@H:35]([NH:38][CH2:46][CH:47]([F:49])[F:48])[CH2:34][CH2:33]2)[N:25]2[CH:30]=[CH:29][N:28]=[C:27]([CH3:31])[C:26]=12

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 1361862-Bromo-1,1-difluoroethane2×HCID 178432913HCID 178432913, compoundHCID 178523781HCID 178523781, compound

Product 1

HCID 178432914HCID 178432914, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Using the procedures described in example 17 (trans)-4-(benzyloxycarbonylamino)cyclohexanecarboxylic acid was used to prepare (trans)-4-(1-bromo-8-methylimidazo[1,5-a]pyrazin-3-yl)cyclohexanamine. The latter compound (0.217 mmol, 67.1 mg) was dissolved in N,N-dimethylformamide, potassium carbonate (0.651 mmol, 90 mg) was added followed by 2-bromo-1,1-difluoroethane (0.217 mmol, 17.47 μl, 31.5 mg) and the reaction mixture was stirred in the micro wave at 60° C. After one hour another amount of 2-bromo-1,1-difluoroethane (0.217 mmol, 17.47 μl, 31.5 mg) was added and the reaction mixture was stirred in the micro wave at 60° C. for another hour. The reaction mixture was filtered, the filter was rinsed with acetonitrile and the filtrate was concentrated. The residue was purified by column chromatography (silica gel, gradient dichloromethane/methanol 10/0 to 9/1) to give (trans)-4-(1-bromo-8-methylimidazo[1,5-a]pyrazin-3-yl)-N-(2,2-difluoroethyl)cyclohexanamine (39.8 mg).

Workup

  1. stirringthe reaction mixture was stirred in the micro wave at 60° C. for another hour
  2. filtrationThe reaction mixture was filtered
  3. washthe filter was rinsed with acetonitrile
  4. concentrationthe filtrate was concentrated
  5. customThe residue was purified by column chromatography (silica gel, gradient dichloromethane/methanol 10/0 to 9/1)

Sources & evidence

ORD record
ord-164193d9d89c492e98c0d33be28e97c2
Source dataset
uspto-grants-2014_02
Patent number
US08658794B2

Reaction notes

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