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

HRID 554139Notes

Reaction equation

HRID 554139 reaction equation
[O:1]=[C:2]1[N:6]([CH2:7][C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=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:9]=[N:10][CH:11]=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 52242072-Chloro-3-(trifluoromethyl)benzylamineHCID 105368875-Oxo-1-(3-pyridinylmethyl)proline

Product 1

HCID 67459890N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-5-oxo-1-(3-pyridinylmethyl)prolinamideYield 7.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-oxo-1-(3-pyridinylmethyl)proline (0.210 g, 1 mmol, prepared as described below), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.383 g, 2 mmol), and 1-hydroxybenzotriazole (0.306 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. The aqueous layer was separated and extracted with more ethyl acetate and then the combined ethyl acetate fractions were washed sequentially with 3 portions of water and then with saturated aqueous sodium chloride solution. Drying over magnesium sulphate and concentration gave a solid residue which was purified by mass-directed automated HPLC to give pure N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-5-oxo-1-(3-pyridinylmethyl)prolinamide (0.031 g).

Workup

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

Sources & evidence

ORD record
ord-6d741a047101425fa6f78629c2367629
Source dataset
uspto-grants-2011_11
Patent number
US08048907B2

Reaction notes

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