Water → HCID 86686804, compound

HRID 1403161Notes

Reaction equation

HRID 1403161 reaction equation
[F:1][CH:2]([F:32])[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:20][CH:21]3[CH2:26][CH2:25][CH2:24][CH:23]([NH2:27])[CH2:22]3)[N:9]=2)[C:6]2[CH:28]=[CH:29][CH:30]=[CH:31][C:5]=2[N:4]=1.C(N([CH2:38][CH3:39])CC)C.O.[CH3:41][C:42](N(C)C)=[O:43]>>[F:32][CH:2]([F:1])[C:3]1[N:7]([C:8]2[CH:13]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:11]=[C:10]([NH:20][CH:21]3[CH2:26][CH2:25][CH2:24][CH:23]([N:27]4[CH2:39][CH2:38][O:43][CH2:42][CH2:41]4)[CH2:22]3)[N:9]=2)[C:6]2[CH:28]=[CH:29][CH:30]=[CH:31][C:5]=2[N:4]=1

Participants

5

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31374DimethylacetamideHCID 86686805HCID 86686805, compound

Product 1

HCID 86686804HCID 86686804, compound

Conditions

Temperature
120 °C

Procedure

To a solution of N-{4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)pyrimidin-2-yl}cyclohexane-1,3-diamine (70 mg) in dimethylacetamide (1.4 mL) were added triethylamine (56 μL) and bis(2-bromomethyl)ether (31 μL), followed by stirring at 120° C. for 2 hours using a microwave reactor. To the reaction solution was added water, followed by extraction with ethyl acetate. The extracts were washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, the desiccant was removed by filtration, and then the solvent was evaporated under reduced pressure. The residue was purified by amino silica gel column chromatography (hexane:ethyl acetate=60:40-20:80) to obtain 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-N-[3-(morpholin-4-yl)cyclohexyl]pyrimidin-2-amine (42 mg).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe extracts were washed with water and saturated brine
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. customthe desiccant was removed by filtration
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by amino silica gel column chromatography (hexane:ethyl acetate=60:40-20:80)

Sources & evidence

ORD record
ord-98bd4a809c8942c3a70e77f328dcd295
Source dataset
uspto-grants-2014_12
Patent number
US08912180B2

Reaction notes

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