Dimethylformamide → HCID 10167774, compound

HRID 1835585Notes

Reaction equation

HRID 1835585 reaction equation
Cl.[C:2]([C:5]1[CH:6]=[CH:7][C:8]([C:38]2[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][CH:39]=2)=[C:9]([CH:37]=1)[CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[N:22]([CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[C:21]3[CH:29]=[CH:30][C:31]([C:33]([O:35][CH3:36])=[O:34])=[CH:32][C:20]=3[N:19]=2)=[CH:14][CH:13]=1)(O)=[O:3].C(Cl)(=O)C(Cl)=O.[CH3:51][N:52](C)C=O>ClCCl>[Cl:44][C:41]1[CH:42]=[CH:43][C:38]([C:8]2[CH:7]=[CH:6][C:5]([C:2](=[O:3])[NH:52][CH3:51])=[CH:37][C:9]=2[CH2:10][O:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]3[N:22]([CH:23]4[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)[C:21]4[CH:29]=[CH:30][C:31]([C:33]([O:35][CH3:36])=[O:34])=[CH:32][C:20]=4[N:19]=3)=[CH:16][CH:17]=2)=[CH:39][CH:40]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 10211420HCID 10211420, compound

Product 1

HCID 10167774HCID 10167774, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl 2-{4-[5-carboxy-2-(4-chlorophenyl benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride (400 mg) obtained in Example 246 was suspended in dichloromethane (5 ml), and oxalyl chloride (0.08 ml) and dimethylformamide (catalytic amount) were added. The mixture was stirred for 2 hr at room temperature. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in dichloromethane (5 ml). The resulting solution was added dropwise to a mixed solution of 40% aqueous methylamine solution (5 ml) and tetrahydrofuran (5 ml) under ice-cooling. The reaction mixture was stirred for 1 hr and concentrated under reduced pressure. Water was added to the residue and the mixture was extracted with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium hydrogencarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was crystallized from ethyl acetate and diisopropyl ether. The crystals were collected by filtration and dried under reduced pressure to give the title compound (335 mg, yield 86%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in dichloromethane (5 ml)
  3. additionThe resulting solution was added dropwise to a mixed solution of 40% aqueous methylamine solution (5 ml) and tetrahydrofuran (5 ml) under ice-
  4. temperaturecooling
  5. stirringThe reaction mixture was stirred for 1 hr
  6. concentrationconcentrated under reduced pressure
  7. additionWater was added to the residue
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe organic layer was washed with water, saturated aqueous sodium hydrogencarbonate and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customthe residue was crystallized from ethyl acetate and diisopropyl ether
  13. filtrationThe crystals were collected by filtration
  14. customdried under reduced pressure

Sources & evidence

ORD record
ord-ef302c65fe834186ab4a95aecc549b81
Source dataset
uspto-grants-2004_08
Patent number
US06770666B2

Reaction notes

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