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

HRID 2238473Notes

Reaction equation

HRID 2238473 reaction equation
[O:1]=[C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C@H:5]([C:14]([OH:16])=O)[CH2:4][CH2:3]1.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[Cl:34][C:35]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:36]=1[CH2:42][NH2:43].Cl.CN(C)CCCN=C=NCC>ClCCl>[Cl:34][C:35]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:36]=1[CH2:42][NH:43][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]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 1399092-Chloro-4-fluorobenzylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10900113(S)-1-Benzyl-5-carboxy-2-pyrrolidinone

Product 1

HCID 49864914N-[(2-chloro-4-fluorophenyl)methyl]-5-oxo-1-(phenylmethyl)prolinamideYield 38.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

5-Oxo-1-(phenylmethyl)-proline (0.176 g, 0.80 mmol, prepared as described below) was dissolved in dichloromethane (3 ml) and to this was added 1-hydroxybenzotriazole (0.119 g, 0.88 mmol), triethylamine (0.113 ml, 0.81 mmol), [(2-chloro-4-fluorophenyl)methyl]amine (0.134 g, 0.84 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.169 g, 0.88 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]-5-oxo-1-(phenylmethyl)-prolinamide (0.112 g) as a white solid.

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-cc52c0ac93524e15848073c509a36259
Source dataset
uspto-grants-2010_05
Patent number
US07718693B2

Reaction notes

Loading…