1-Hydroxybenzotriazole → N-[(2-chloro-4-fluorophenyl)methyl]-1-(1-methylethyl)-5-oxo-prolinamide

HRID 2238475Notes

Reaction equation

HRID 2238475 reaction equation
[CH3:1][CH:2]([N:4]1[C:11](=[O:12])[CH2:10][CH2:9][C@H:5]1[C:6]([OH:8])=O)[CH3:3].ON1C2C=CC=CC=2N=N1.[Cl:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[CH2:31][NH2:32].Cl.CN(C)CCCN=C=NCC>ClCCl.CN(C)C=O>[Cl:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[CH2:31][NH:32][C:6](=[O:8])[C@@H:5]1[CH2:9][CH2:10][C:11](=[O:12])[N:4]1[CH:2]([CH3:1])[CH3:3]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 1399092-Chloro-4-fluorobenzylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 18649401(S)-1-isopropyl-5-oxopyrrolidine-2-carboxylic acid

Product 1

HCID 49864875N-[(2-chloro-4-fluorophenyl)methyl]-1-(1-methylethyl)-5-oxo-prolinamideYield 29.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

1-(1-Methylethyl)-5-oxo-proline (0.060 g, 0.35 mmol, prepared as described below) was dissolved in dichloromethane (3 ml) and dimethylformamide (1 ml) and to this was added 1-hydroxybenzotriazole (0.052 g, 0.39 mmol), [(2-chloro-4-fluorophenyl)methyl]amine (0.061 g, 0.39 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.074 g, 0.39 mmol) under an atmosphere of argon. The mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane and washed sequentially with 2M aqueous hydrogen chloride and saturated aqueous sodium hydrogen carbonate. The organic layer was filtered through a phase separator and then evaporated to give the crude product. The crude material was purified by mass-directed automated HPLC to give pure N-[(2-chloro-4-fluorophenyl)methyl]-1-(1-methylethyl)-5-oxo-prolinamide (0.032 g) as a white solid. LC/MS [M+H]+=313.1, retention time=2.26 minutes.

Workup

  1. washwashed sequentially with 2M aqueous hydrogen chloride and saturated aqueous sodium hydrogen carbonate
  2. filtrationThe organic layer was filtered through a phase separator
  3. customevaporated
  4. customto give the crude product
  5. customThe crude material was purified

Sources & evidence

ORD record
ord-0a4092ccece8461f945b91325102948e
Source dataset
uspto-grants-2010_05
Patent number
US07718693B2

Reaction notes

Loading…