Hydrochloric Acid → HCID 69473945, compound

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Reaction Steps

Thiazino-quinolinone compounds (e.g., Structure 56) are prepared as shown in Scheme XI. The process of Scheme XI begins with the treatment of an aniline, for example, 4-bromo-3-chloroaniline, with a β-ketoester or its corresponding hydrate, for example 4,4,4-trifluoroacetoacetate, at elevated temperatures, to afford the corresponding acetanilide. Treatment of the acetanilide with an acid, for example, sulfuric acid, affords the corresponding 1H-quinolin-2-one (an example of a Knorr cyclization as described further herein). Protection of the pyridone ring, with, for example, isopropyl iodide, mediated by a base, for example, cesium fluoride, affords a compound of Structure 51. Treatment of a compound (e.g., Structure 51) with a β-aminothiol, for example, 2-aminoethanethiol hydrochloride, mediated by a base, for example, sodium hydride, affords a compound of Structure 52. Treatment of a compound of Structure 52 with a ligated transition metal. for example palladium acetate and BINAP, in the presence of a base, for example sodium t-butoxide, at elevated temperatures, affords a compound of Structure 53, See S. Wagaw, et al., J. Am. Chem. Soc. 1997, 119, 8451-8458. Treatment of a compound of Structure 53 with an aldehyde or its corresponding hydrate or hemiacetal, for example, formaldehyde, affords a compound of Structure 55. Hydrolysis of the imino ether can be accomplished by treatment of a compound of Structure 55 with an acid, for example hydrochloric acid, at elevated temperatures, to afford a thiazino-quinolinone compound such as Structure 56. Alternatively, a compound of Structure 53 can be deprotected with an acid, for example hydrochloric acid, at elevated temperatures, to afford a thiazino-quinolinone compound such as Structure 54.

Provenance & Evidence