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

HRID 554137Notes

Reaction equation

HRID 554137 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-637cae5869a143f8a514d99c1a923d94
Source dataset
uspto-grants-2011_11
Patent number
US08048907B2

Reaction notes

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