Methyl chloroformate → HCID 54407911, compound

HRID 1934692Notes

Reaction equation

HRID 1934692 reaction equation
Cl[C:2]([O:4][CH3:5])=[O:3].[C:6]([C:8]1[CH:9]=[CH:10][C:11]([NH:28][C@H:29]2[CH2:33][CH2:32][NH:31][CH2:30]2)=[C:12]([CH:27]=1)[C:13]([NH:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([O:25][CH3:26])[CH:18]=1)=[O:14])#[N:7].C(N(CC)CC)C>C(Cl)(Cl)Cl.CN1CCN(C)C1=O>[C:6]([C:8]1[CH:9]=[CH:10][C:11]([NH:28][C@H:29]2[CH2:33][CH2:32][N:31]([C:2]([O:4][CH3:5])=[O:3])[CH2:30]2)=[C:12]([CH:27]=1)[C:13]([NH:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([O:25][CH3:26])[CH:18]=1)=[O:14])#[N:7]

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 54010736HCID 54010736, compound

Product 1

HCID 54407911HCID 54407911, compoundYield 59.7%

Reagents, catalysts & solvents 2

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

Procedure

A solution of methyl chloroformate (26 mg) in chloroform (2 mL) was added dropwise to a mixture of (S)-5-cyano-N-(3,4-dimethoxybenzyl)-2-(3-pyrrolidinylamino)benzamide (80 mg) and triethylamine (43 mg) in a mixture of chloroform (2 mL) and 1,3-dimethyl-2-imidazolidinone (1 mL) under cooling on an ice bath. The reaction mixture was stirred for 2 hours at same temperature and the reaction was quenched by addition of 3-(N,N-dimethylamino)propylamine (0.1 mL). The mixture was concentrated in vacuo, and the residue was partitioned between ethyl acetate and 3.6% hydrochloric acid. The organic layer was washed with an aqueous saturated sodium bicarbonate solution and brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by a silica gel column chromatography eluting with 70% ethyl acetate in hexane. The obtained crystals were recrystallized from a mixture of 2-propanol and diisopropyl ether to give (S)-5-cyano-N-(3,4-dimethoxybenzyl)-2-[1-(methoxycarbonyl)pyrrolidin-3-ylamino]benzamide (55 mg) as white crystals.

Workup

  1. temperatureunder cooling on an ice bath
  2. customthe reaction was quenched by addition of 3-(N,N-dimethylamino)propylamine (0.1 mL)
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe residue was partitioned between ethyl acetate and 3.6% hydrochloric acid
  5. washThe organic layer was washed with an aqueous saturated sodium bicarbonate solution and brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography
  9. washeluting with 70% ethyl acetate in hexane
  10. customThe obtained crystals were recrystallized from a mixture of 2-propanol and diisopropyl ether

Sources & evidence

ORD record
ord-2021d8c60ff441cd928058122af58d64
Source dataset
uspto-grants-2002_05
Patent number
US06384080B1

Reaction notes

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