Potassium Carbonate → HCID 86686766, compound

HRID 1403137Notes

Reaction equation

HRID 1403137 reaction equation
[F:1][CH:2]([F:28])[C:3]1[N:7]([C:8]2[CH:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10](S(C)(=O)=O)[N:9]=2)[C:6]2[CH:24]=[CH:25][CH:26]=[CH:27][C:5]=2[N:4]=1.[NH2:29][C@H:30]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31]1.C(=O)([O-])[O-].[K+].[K+].CN(C)C(=O)C>O>[F:1][CH:2]([F:28])[C:3]1[N:7]([C:8]2[CH:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([NH:29][C@H:30]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31]3)[N:9]=2)[C:6]2[CH:24]=[CH:25][CH:26]=[CH:27][C:5]=2[N:4]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 31374DimethylacetamideHCID 854071tert-butyl (3S)-3-aminopyrrolidine-1-carboxylateHCID 67980988HCID 67980988, compound

Product 1

HCID 86686766HCID 86686766, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-difluoromethyl-1-[2-(methylsulfonyl)-6-morpholin-4-ylpyrimidin-4-yl]-1H-benzimidazole (770 mg), tert-butyl (3S)-3-aminopyrrolidine-1-carboxylate (525 mg), potassium carbonate (390 mg), and N,N-dimethylacetamide (19 mL) was stirred in a microwave reactor at 100° C. for 1 hour. The reaction mixture was cooled to room temperature and then poured into water, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and then the residue was purified by amino silica gel column chromatography (hexane:ethyl acetate=80:20-50:50) to obtain tert-butyl (3S)-3-({4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-morpholin-4-ylpyrimidin-2-yl}amino)pyrrolidine-1-carboxylate (310 mg) as a pale yellow amorphous substance.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by amino silica gel column chromatography (hexane:ethyl acetate=80:20-50:50)

Sources & evidence

ORD record
ord-d21c2db08bd44c37a41776367903ffc1
Source dataset
uspto-grants-2014_12
Patent number
US08912180B2

Reaction notes

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