Potassium Carbonate → 2-(difluoromethyl)-1-[4-(3-methoxyprop-1-yn-1-yl)-6-(morpholin-4-yl)pyrimidin-2-yl]-1H-benzimidazole

HRID 1403149Notes

Reaction equation

HRID 1403149 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]=[C:15]2[CH:23]([F:25])[F:24])[N:3]=1.[CH3:26][O:27][CH2:28][C:29]#[CH:30].C(=O)([O-])[O-].[K+].[K+].[Cl-].[NH4+]>CN(C)C=O.[Cu]I.C(Cl)(Cl)Cl>[F:24][CH:23]([F:25])[C:15]1[N:14]([C:4]2[N:3]=[C:2]([C:30]#[C:29][CH2:28][O:27][CH3:26])[CH:7]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:5]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 693933-MethoxypropyneHCID 442492591-[4-chloro-6-(4-morpholinyl)-2-pyrimidinyl]-2-(difluoromethyl)-1H-benzimidazole

Product 1

HCID 866867852-(difluoromethyl)-1-[4-(3-methoxyprop-1-yn-1-yl)-6-(morpholin-4-yl)pyrimidin-2-yl]-1H-benzimidazole

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

1-[4-Chloro-6-(morpholin-4-yl)pyrimidin-2-yl]-2-(difluoromethyl)-1H-benzimidazole (100 mg) was dissolved in dimethylformamide (1 mL), and 3-methoxyprop-1-yne (45 μL), tetrakistriphenylphosphine palladium (0) (16 mg), copper (I) iodide (1.3 mg), and potassium carbonate (227 mg) were added thereto, followed by stirring in a microwave reactor at 80° C. for 1 hour. An aqueous ammonium chloride solution and chloroform were added thereto, and the organic layer was extracted, washed with saturated brine, and then dried over anhydrous magnesium sulfate. Then, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=60:40). A mixed solvent of diisopropyl ether and hexane was added thereto, and the resulting solid was collected by filtration and further washed with hexane to obtain 2-(difluoromethyl)-1-[4-(3-methoxyprop-1-yn-1-yl)-6-(morpholin-4-yl)pyrimidin-2-yl]-1H-benzimidazole (10 mg) as a yellow powder.

Workup

  1. extractionthe organic layer was extracted
  2. washwashed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThen, the solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=60:40)
  6. additionA mixed solvent of diisopropyl ether and hexane was added
  7. filtrationthe resulting solid was collected by filtration
  8. washfurther washed with hexane

Sources & evidence

ORD record
ord-39609f8d463b41a9b92442dc21b679aa
Source dataset
uspto-grants-2014_12
Patent number
US08912180B2

Reaction notes

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