Acetonitrile → HCID 86603858, compound

HRID 2217309Notes

Reaction equation

HRID 2217309 reaction equation
[CH2:1]([O:3][CH:4]([C:21]1[C:30]([O:31][CH3:32])=[CH:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=1)[N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[NH:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)[CH3:2].[C:33](=[O:36])([O-])[O-:34].[K+].[K+].[C:39](#[N:41])[CH3:40]>CN(C=O)C>[CH2:1]([O:3][CH:4]([C:21]1[C:30]([O:31][CH3:32])=[CH:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=1)[N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[NH:14][CH:15]1[CH2:20][CH2:19][N:18]([CH2:40][CH:39]([NH:41][C:33](=[O:36])[O:34][C:28]([CH3:29])([CH3:23])[CH3:27])[CH:8]([CH3:13])[CH3:9])[CH2:17][CH2:16]1)[CH3:2]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 22036985HCID 22036985, compound

Product 1

HCID 86603858HCID 86603858, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

Intermediate (32) (0.1382 mol) was added at 55° C. to a mixture of (±)-1-[ethoxy(3-methoxy-2-quinolinyl)methyl]-N-(4-piperidinyl)-1H-benzimidazol-2-amine (0.0346 mol) and potassium carbonate (0.242 mol) in acetonitrile (108 ml) and DMF (20 ml) (1 equiv of intermediate (32) was added every hour). The mixture was stirred at 55° C. for 1 hour and filtered. The filtrate was poured out into H2O and the mixture was extracted with EtOAc. The organic layer was separated, washed with a saturated NaCl solution, dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 98/2/0.4 and 96/4/0.5; 20-45 μm). Two fractions were collected and their solvents were evaporated, yielding 2.5 g (23%) of (±)-1,1-dimethylethyl [1-[[4-[[1-[ethoxy(3-methoxy-2-quinolinyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]methyl]-2-methylpropyl]carbamate (comp. 38).

Workup

  1. additionwas added every hour)
  2. filtrationfiltered
  3. additionThe filtrate was poured out into H2O
  4. extractionthe mixture was extracted with EtOAc
  5. customThe organic layer was separated
  6. washwashed with a saturated NaCl solution
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent was evaporated
  10. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 98/2/0.4 and 96/4/0.5; 20-45 μm)
  11. customTwo fractions were collected
  12. customtheir solvents were evaporated

Sources & evidence

ORD record
ord-1f84c82dabcf4505853d130cd10d5acd
Source dataset
uspto-grants-2008_08
Patent number
US07407969B2

Reaction notes

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