Water → 2-Isopropylaminothiazole-4-carboxylic acid [6-acetyl-2-chloro-3-(2,2-dimethoxyethoxy)phenyl]amide

Participants

Reaction Conditions

Reaction Steps

To a mixture of 1-[2-amino-3-chloro-4-(2,2-dimethoxyethoxy)phenyl]ethanone (13 g, 47.5 mmol) and isopropylaminothiazole-4-carboxylic acid hydrobromide (prepared as described in Ivanov, V., et. al.; EP1881001A1, p. 62-63; 12.6 g, 47.5 mmol) in pyridine (150 ml) was slowly added phosphorus oxychloride (9.47 g, 61.8 mmol) at −40° C. The mixture was then stirred at 0° C. for 4 h. Upon completion of the reaction, H2O (30 ml) was added dropwise to the mixture. The mixture was then stirred at 0° C. for another 15 min. The mixture was concentrated in vacuo. The residue was diluted with EtOAc, washed with a sat. NaHCO3 aqueous solution. The organic layer was dried (Na2SO4) and concentrated in vacuo. The residue was dissolved in CH2Cl2, hexanes was added slowly to the solution, and a yellow solid started to crash out. More hexanes were added precipitation was complete to afford 2-isopropylaminothiazole-4-carboxylic acid [6-acetyl-2-chloro-3-(2,2-dimethoxyethoxy)phenyl]amide (18 g, 85% yield).

Provenance & Evidence