Triethylamine → HCID 178423374, compound

HRID 1403162Notes

Reaction equation

HRID 1403162 reaction equation
[F:1][CH:2]([F:33])[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][C@H:21]3[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23][CH2:22]3)[N:9]=2)[C:6]2[CH:28]=[C:29]([CH3:32])[CH:30]=[CH:31][C:5]=2[N:4]=1.C(N(CC)CC)C.Cl[CH2:42][CH2:43][CH2:44][C:45](Cl)=[O:46]>C(Cl)Cl>[F:33][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][C@H:21]3[CH2:22][CH2:23][C@H:24]([N:27]4[CH2:42][CH2:43][CH2:44][C:45]4=[O:46])[CH2:25][CH2:26]3)[N:9]=2)[C:6]2[CH:28]=[C:29]([CH3:32])[CH:30]=[CH:31][C:5]=2[N:4]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 783704-Chlorobutyryl chlorideHCID 178423375HCID 178423375, compound

Product 1

HCID 178423374HCID 178423374, compoundYield 69.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of trans-N-{4-[2-(difluoromethyl)-6-methyl-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)pyrimidin-2-yl}cyclohexane-1,4-diamine (50 mg) in methylene chloride (1 mL) were added triethylamine (46 μL) and 4-chlorobutyryl chloride (16 mg), followed by stirring for 1 hour in a water bath. The reaction solution was concentrated under reduced pressure and to the residue were added tetrahydrofuran (5 mL) and 60% sodium hydride (13 mg), followed by stirring at 0° C. for 30 minutes and at room temperature for 1 hour. To the reaction solution was added water, followed by extraction with ethyl acetate, and the extracts were washed with water and saturated brine, and 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=50:50-0:100 and chloroform:methanol=100:0-90:10) to obtain 1-[trans-4-({4-[2-(difluoromethyl)-6-methyl-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)pyrimidin-2-yl}amino)cyclohexyl]pyrrolidin-2-one (40 mg).

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure and to the residue
  2. additionwere added tetrahydrofuran (5 mL) and 60% sodium hydride (13 mg)
  3. stirringby stirring at 0° C. for 30 minutes and at room temperature for 1 hour
  4. additionTo the reaction solution was added water
  5. extractionfollowed by extraction with ethyl acetate
  6. washthe extracts were washed with water and saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe desiccant was removed by filtration
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by amino silica gel column chromatography (hexane:ethyl acetate=50:50-0:100 and chloroform:methanol=100:0-90:10)

Sources & evidence

ORD record
ord-5644c3b4679448f1bf0b9488f76c18c9
Source dataset
uspto-grants-2014_12
Patent number
US08912180B2

Reaction notes

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