Methyl chloroformate → HCID 70017309, compound

HRID 1370144Notes

Reaction equation

HRID 1370144 reaction equation
Cl[C:2]([O:4][CH3:5])=[O:3].[Cl:6][C:7]1[CH:8]=[C:9]([CH:28]=[CH:29][C:30]=1[O:31][CH3:32])[CH2:10][N:11]1[C:15]2[CH:16]=[C:17]([C:20]#[N:21])[CH:18]=[CH:19][C:14]=2[N:13]([C@H:22]2[CH2:26][CH2:25][NH:24][CH2:23]2)[C:12]1=[O:27].C(N(CC)CC)C>C(Cl)(Cl)Cl.CN1CCN(C)C1=O>[Cl:6][C:7]1[CH:8]=[C:9]([CH:28]=[CH:29][C:30]=1[O:31][CH3:32])[CH2:10][N:11]1[C:15]2[CH:16]=[C:17]([C:20]#[N:21])[CH:18]=[CH:19][C:14]=2[N:13]([C@H:22]2[CH2:26][CH2:25][N:24]([C:2]([O:4][CH3:5])=[O:3])[CH2:23]2)[C:12]1=[O:27]

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 70015775HCID 70015775, compound

Product 1

HCID 70017309HCID 70017309, compoundYield 59.7%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 66611,3-Dimethyl-2-imidazolidinoneSolvent

Procedure

A solution of methyl chloroformate (25.7 mg) in chloroform (1 ml) was added dropwise to a mixture of 3-(3-chloro-4-methoxybenzyl)-5-cyano-1-[(S)-pyrrolidin-3-yl]-2,3-dihydro-1H-benzimidazole-2-one (80 mg) and triethylamine (31.7 mg) in a mixture of chloroform (1.6 ml) and 1,3-dimethyl-2-imidazolidinone (0.8 ml) under cooling on an ice bath. The reaction mixture was stirred at same temperature for 2 hours and quenched by addition of 3-(N,N-diethylamino)propylamine (0.1 ml). The mixture was poured into water and extracted with chloroform. The organic layer was washed with 1N-hydrochloric acid, water, an aqueous saturated sodium bicarbonate solution and brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by a preparative thin layer chromatography (10% methanol in chloroform) to give 3-(3-chloro-4-methoxybenzyl)-5-cyano-1-[(S)-1-methoxycarbonylpyrrolidin-3-yl]-2,3-dihydro-1H-benzimidazole-2-one (55 mg).

Workup

  1. temperatureunder cooling on an ice bath
  2. customquenched by addition of 3-(N,N-diethylamino)propylamine (0.1 ml)
  3. additionThe mixture was poured into water
  4. extractionextracted with chloroform
  5. washThe organic layer was washed with 1N-hydrochloric acid, water
  6. dry with materialan aqueous saturated sodium bicarbonate solution and brine, dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a preparative thin layer chromatography (10% methanol in chloroform)

Sources & evidence

ORD record
ord-002bc68e00f84b11897781b48a2e322d
Source dataset
uspto-grants-2003_06
Patent number
US06582351B1

Reaction notes

Loading…