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

HRID 554069Notes

Reaction equation

HRID 554069 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-11c494b10288406a98e344231437ca90
Source dataset
uspto-grants-2011_11
Patent number
US08048907B2

Reaction notes

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