Oxalyl chloride → N-(5-benzyloxy-pyridin-2-yl)-3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionamide

HRID 398494Notes

Reaction equation

[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[CH2:25]([O:32][C:33]1[CH:34]=[CH:35][C:36]([NH2:39])=[N:37][CH:38]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C)C=O>[CH2:25]([O:32][C:33]1[CH:34]=[CH:35][C:36]([NH:39][C:8](=[O:10])[CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)=[N:37][CH:38]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionic acid (prepared as in Example 38A, 183 mg, 0.63 mmol) in methylene chloride (6.37 mL) was cooled to 0° C. and then treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.35 mL, 0.7 mmol) and a few drops of N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 10 min and then at 25° C. for 30 min. The reaction mixture was then treated with 5-benzyloxy-pyridin-2-ylamine (281 mg, 1.4 mmol) and N,N-diisopropylethylamine (0.26 mL, 1.5 mmol). The reaction mixture was stirred at 25° C. for 16 h. At this time, the reaction was concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 70/30 hexanes/ethyl acetate) afforded N-(5-benzyloxy-pyridin-2-yl)-3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionamide (150 mg, 50.0%) as a yellow solid: mp 47-49° C.; EI-HRMS m/e calcd for C26H26Cl2N2O2 (M+) 469.1449, found 469.1455.

Workup

waitat 25° C. for 30 min
stirringThe reaction mixture was stirred at 25° C. for 16 h
concentrationAt this time, the reaction was concentrated in vacuo

Sources & evidence

ORD record: ord-2a83c05f51aa45f4ac9b542db7871f23
Source dataset: uspto-grants-2003_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06610846B1

Reaction notes

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