Dimethylformamide → HCID 86686774, compound

HRID 1403141Notes

Reaction equation

HRID 1403141 reaction equation
[ClH:1].Cl.[F:3][CH:4]([F:32])[C:5]1[N:9]([C:10]2[CH:15]=[C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[N:13]=[C:12]([NH:22][C@H:23]3[CH2:27][CH2:26][NH:25][CH2:24]3)[N:11]=2)[C:8]2[CH:28]=[CH:29][CH:30]=[CH:31][C:7]=2[N:6]=1.CN(C)C=O.[CH3:38][N:39]([CH3:43])[CH2:40][CH2:41]Br.C(=O)([O-])[O-].[K+].[K+]>O>[ClH:1].[ClH:1].[F:32][CH:4]([F:3])[C:5]1[N:9]([C:10]2[CH:15]=[C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[N:13]=[C:12]([NH:22][C@H:23]3[CH2:27][CH2:26][N:25]([CH2:41][CH2:40][N:39]([CH3:43])[CH3:38])[CH2:24]3)[N:11]=2)[C:8]2[CH:28]=[CH:29][CH:30]=[CH:31][C:7]=2[N:6]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 178642-BromoethyldimethylamineHCID 86686768HCID 86686768, compound

Product 1

HCID 86686774HCID 86686774, compoundYield 23.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-morpholin-4-yl-N-[(3S)-pyrrolidin-3-yl]pyrimidin-2-amine dihydrochloride (75 mg) and N,N-dimethylformamide (1.5 mL) were added 2-(dimethylamino)ethyl bromide (26 mg) and potassium carbonate (85 mg), and the mixture was stirred at room temperature overnight. To the reaction mixture was added 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=50:50-0:100, and subsequently chloroform:methanol=100:0-80:20). Desired fractions are combined and concentrated under reduced pressure. The residue was dissolved in 1,4-dioxane (0.5 mL) and a 4 M solution (80 μL) of hydrogen chloride in 1,4-dioxane was added thereto. Diisopropyl ether (10 mL) was further added thereto. The resulting powder was collected by filtration, washed with diisopropyl ether, and dried under reduced pressure to obtain 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-N-{(3S)-1-[2-(dimethylamino)ethyl]pyrrolidin-3-yl}-6-morpholin-4-ylpyrimidin-2-amine dihydrochloride (10 mg) as a white powder.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by amino silica gel column chromatography (hexane
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in 1,4-dioxane (0.5 mL)
  8. additiona 4 M solution (80 μL) of hydrogen chloride in 1,4-dioxane was added
  9. additionDiisopropyl ether (10 mL) was further added
  10. filtrationThe resulting powder was collected by filtration
  11. washwashed with diisopropyl ether
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-6ffbded9c34f4801bb8f05286e272a87
Source dataset
uspto-grants-2014_12
Patent number
US08912180B2

Reaction notes

Loading…