Hydrochloric Acid → 3-Fluoro-4-[[2-(2-pyridinylamino)-5-thiazolyl]thio]-2-pyridinecarboxylic acid

Participants

Reaction Conditions

Reaction Steps

A DMF (3 mL) solution of methyl 4-chloro-3-fluoropicolinate (0.3 g, 1.58 mmol) was bubbled 10 min with argon, then sodium hydrogensulfide hydrate (0.146 g, 1.98 mmol, 1.25 eq) was added and the mixture was gently heated to 37° C. The mixture was diluted with methanol then 5-bromo-N-(pyridin-2-yl)thiazol-2-amine (0.404 g, 1.58 mmol, 1 eq, described in the synthesis of thiazoles Example A) was added, followed by a solution of sodium methoxide 25% (0.725 mL, 3.16 mmol, 2 eq). The mixture was heated at 65° C. for 1 h, cooled to 23° C., diluted with water (5 ml) and stirred 5 days. The mixture was neutralized with HCl 1N, concentrated to dryness, suspended in water, sonicated and the resulting solid was collected by filtration. The solid was purified on preparative HPLC (TFA/water/acetonitrile) and the fractions were concentrated on speedvac to give the title compound as a solid (0.023 g, 4%). The compound was used as such in the next step.

Provenance & Evidence