Phosphorus oxychloride → 2-Isopropyl-thiazole-4-carboxylic acid [6-acetyl-2-chloro-3-(2,2-dimethoxy-ethoxy)-phenyl]-amide

HRID 1422524Notes

Reaction equation

[NH2:1][C:2]1[C:7]([Cl:8])=[C:6]([O:9][CH2:10][CH:11]([O:14][CH3:15])[O:12][CH3:13])[CH:5]=[CH:4][C:3]=1[C:16](=[O:18])[CH3:17].[CH:19]([C:22]1[S:23][CH:24]=[C:25]([C:27](O)=[O:28])[N:26]=1)([CH3:21])[CH3:20].O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[C:16]([C:3]1[C:2]([NH:1][C:27]([C:25]2[N:26]=[C:22]([CH:19]([CH3:21])[CH3:20])[S:23][CH:24]=2)=[O:28])=[C:7]([Cl:8])[C:6]([O:9][CH2:10][CH:11]([O:12][CH3:13])[O:14][CH3:15])=[CH:5][CH:4]=1)(=[O:18])[CH3:17]

Participants

Conditions

Temperature: -10 °C

Procedure

1-[2-amino-3-chloro-4-(2,2-dimethoxy-ethoxy)phenyl]-ethanone (3.98 g, 14.6 mmol) and 2-isopropyl-thiazole-4-carboxylic acid (2.5 g, 14.6 mmol) was dissolved in pyridine (40 mL) and was cooled to −10° C. POCl3 (1.74 mL, 19.0 mmol) was added dropwise. The reaction was stirred at −10° C. for 2 hours. The reaction was quenched with CH3OH (5 mL). After 15 minutes, the reaction was taken up in EtOAc and extracted with 2N HCl(aq). The organic layer was dried with Na2SO4, filtered and was concentrated. 2-Isopropyl-thiazole-4-carboxylic acid [6-acetyl-2-chloro-3-(2,2-dimethoxy-ethoxy)-phenyl]-amide (5.58 g, 89%) was isolated by silica gel chromatography as a white solid.

Workup

customThe reaction was quenched with CH3OH (5 mL)
waitAfter 15 minutes
extractionextracted with 2N HCl(aq)
dry with materialThe organic layer was dried with Na2SO4
filtrationfiltered
concentrationwas concentrated

Sources & evidence

ORD record: ord-73e2e1cce3bf4b11a8c7771358422e1a
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927484B2

Reaction notes

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