Oxalyl chloride → 6-[3-Cyclopentyl-2-(4-nitro-phenyl)-propionylamino]-nicotinic acid methyl ester

HRID 2296957Notes

Reaction equation

[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[CH3:26][O:27][C:28](=[O:36])[C:29]1[CH:34]=[CH:33][C:32]([NH2:35])=[N:31][CH:30]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C)C=O.O1CCCC1>[CH3:26][O:27][C:28](=[O:36])[C:29]1[CH:34]=[CH:33][C:32]([NH:35][C:8](=[O:10])[CH:7]([C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)[CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)=[N:31][CH:30]=1

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of 3-cyclopentyl-2-(4-nitro-phenyl)-propionic acid (prepared in Example 1, 526 mg, 2.0 mmol) in methylene chloride (20 mL) was cooled to 0° C. and then treated with a 2.0M solution of oxalyl chloride in methylene chloride (1.2 mL, 2.4 mmol) and a few drops of N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 10 min and at 25° C. for 30 min. The reaction mixture was then treated with a solution of 6-amino-nicotinic acid methyl ester (532 mg, 3.5 mmol) and N,N-diisopropylethylamine (0.84 mL, 4.82 mmol) in tetrahydrofuran (10 mL). The reaction mixture was stirred at 25° C. for 48 h. At this time, the reaction was concentrated in vacuo. High pressure liquid chromatography (Chromegasphere SI-60, 10 μM, 60 Å, 25 cm×23 cm ID, 50/50 heptane/ethyl acetate) afforded 6-[3-cyclopentyl-2-(4-nitro-phenyl)-propionylamino]-nicotinic acid methyl ester (353.9 mg, 44.6%) as a pale orange oil: EI-HRMS m/e calcd for C21H23N3O5 (M+) 397.1637, found 397.1631.

Workup

stirringThe reaction mixture was stirred at 25° C. for 48 h
concentrationAt this time, the reaction was concentrated in vacuo

Sources & evidence

ORD record: ord-46a5005153f0441195f3720bda2105d3
Source dataset: uspto-grants-2002_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06489485B2

Reaction notes

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