Oxalyl chloride → HCID 10185003, compound

HRID 2296949Notes

Reaction equation

HRID 2296949 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)=[O:19])=[CH:13][CH:12]=2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[CH2:32]([O:34][C:35]([C:37]1[N:38]=[C:39]([NH2:42])[S:40][CH:41]=1)=[O:36])[CH3:33].C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C)C=O.O1CCCC1>[CH2:32]([O:34][C:35]([C:37]1[N:38]=[C:39]([NH:42][C:8](=[O:9])[CH:7]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)=[O:19])=[CH:13][CH:12]=2)[CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[S:40][CH:41]=1)=[O:36])[CH3:33]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 73216Ethyl 2-aminothiazole-4-carboxylateHCID 81531DiisopropylethylamineHCID 18388776HCID 18388776, compound

Product 1

HCID 10185003HCID 10185003, compoundYield 12.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-{4-[(pyridine-3-carbonyl)-amino]-phenyl}-propionic acid (233 mg, 0.66 mmol) in methylene chloride (10 mL) was cooled to 0° C. and then treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.36 mL, 0.72 mmol) and a few drops of N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 15 min and at 25° C. for 30 min. The reaction mixture was then treated with a solution of 2-amino-thiazole-4-carboxylic acid ethyl ester (367 mg, 1.45 mmol) in tetrahydrofuran (5 mL) and N,N-diisopropylethylamine (0.40 mL, 2.31 mmol). This solution 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, 95/5 ethyl acetate/heptane) afforded 2-(3-cyclopentyl-2-{4-[(pyridine-3-carbonyl)-amino]-phenyl}propionylamino)-thiazole-4-carboxylic acid ethyl ester (40.5 mg, 12.5%) as an off-white: mp 222-223° C.; EI-HRMS m/e calcd for C26H28N4O4S (M+) 492.1831, found 492.1835.

Workup

  1. stirringThis solution was stirred at 25° C. for 48 h
  2. concentrationAt this time, the reaction was concentrated in vacuo

Sources & evidence

ORD record
ord-55151df140fc4f41be23c4990b9219b1
Source dataset
uspto-grants-2002_12
Patent number
US06489485B2

Reaction notes

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