Hydrochloric Acid → N-(3-Chloro-phenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide

Participants

Reaction Steps

A solution of 0.51 gm (44 millimols) of 3-chloro-aniline in 8 ml of dry tetrahydrofuran was added dropwise to a solution of 2-methyl-4-(1-pyrrolidyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acidchloride-1,1-dioxide in tetrahydrofuran at -40° C. The latter solution was obtained by reacting 0.63 gm (2 millimols) of 2-methyl-4-(1-pyrrolidyl)-2H-naphtho[2,1-e]-1,2-thiazine-1,1-dioxide with 0.25 gm (2.5 millimols) of phosgene and 0.25 gm (2.5 millimols) of triethylamine in 16 ml of anhydrous tetrahydrofuran, as described below. The reaction mixture was allowed to warm to room temperature for 24 hours.Then, ice water was added, and the aqueous mixture was extracted twice withmethylene chloride. The combined organic phases were washed twice with water, dried over sodium sulfate and evaporated in vacuo. Petroleum ether was added to the residue, whereby crude crystalline N-(3-chloro-phenyl)-2-methyl-4-(1-pyrrolidyl)-2H-naphtho[2,1-e]-1,2 -thiazine-3-carboxamide-1,1-dioxide, m.p. 163°-167° C (decomp.), was obtained, which was immediately dissolved in 6 ml of aceticacid, and 2 N hydrochloric acid were added to the solution. The mixture washeated at 100° for 30 minutes, allowed to cool, and 50 ml of ice water were added. The precipitated product was filtered off, dried and recrystallized from ethylene chloride/petroleum ether, yielding 410 mgm (49% of theory) of N-(3-chloro-phenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide, m.p. 247°-248° C (decomp.).

Provenance & Evidence