1-Hydroxybenzotriazole → N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-5-oxo-1-(2-pyridinylmethyl)prolinamide

HRID 2238543Notes

Reaction equation

HRID 2238543 reaction equation
[O:1]=[C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[C@H:5]([C:14]([OH:16])=O)[CH2:4][CH2:3]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[Cl:39][C:40]1[C:45]([C:46]([F:49])([F:48])[F:47])=[CH:44][CH:43]=[CH:42][C:41]=1[CH2:50][NH2:51]>ClCCl>[Cl:39][C:40]1[C:45]([C:46]([F:48])([F:49])[F:47])=[CH:44][CH:43]=[CH:42][C:41]=1[CH2:50][NH:51][C:14](=[O:16])[C@@H:5]1[CH2:4][CH2:3][C:2](=[O:1])[N:6]1[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 52242072-Chloro-3-(trifluoromethyl)benzylamineHCID 421273705-Oxo-1-(2-pyridinylmethyl)proline

Product 1

HCID 67464098N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-5-oxo-1-(2-pyridinylmethyl)prolinamideYield 63.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-oxo-1-(2-pyridinylmethyl)proline (0.220 g, 1 mmol, prepared as described below), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.384 g, 2 mmol), and 1-hydroxybenzotriazole (0.308 g, 2 mmol) were stirred together in dichloromethane (10 ml) at room temperature for 30 minutes. The mixture was then treated with {[2-chloro-3-(trifluoromethyl)phenyl]methyl}amine (0.314 g, 1.5 mmol) and the mixture was stirred overnight at room temperature. The mixture was concentrated and partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate solution. The aqueous layer was separated and extracted with ethyl acetate and then the combined ethyl acetate fractions were washed with 3 portions of water and then with saturated aqueous sodium chloride solution. Drying over sodium sulphate and concentration gave a solid residue which was purified by mass-directed automated HPLC to give N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-5-oxo-1-(2-pyridinylmethyl)prolinamide (0.263 g) as a buff-coloured solid.

Workup

  1. concentrationThe mixture was concentrated
  2. custompartitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate solution
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate
  5. washthe combined ethyl acetate fractions were washed with 3 portions of water
  6. dry with materialDrying over sodium sulphate and concentration
  7. customgave a solid residue which
  8. customwas purified

Sources & evidence

ORD record
ord-76484069a5af4d039cd72b2540812c70
Source dataset
uspto-grants-2010_05
Patent number
US07718693B2

Reaction notes

Loading…