Pyridine → 1-(5-bromo-3-fluoropyridin-2-yl)-N-(6-fluorobenzo[d]thiazol-2-yl)-1,2,3,6-tetrahydropyridine-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

In a 50 mL vial with a screw-top septum, 1.03 grams 1-(5-bromo-3-fluoropyridin-2-yl)-1,2,3,6-tetrahydropyridine-4-carboxylic acid 23 (3.32 mMol) were cooled to 0° C. Ten milliliters thionyl chloride were poured directly onto the solid and stirred until the vial reached room temperature. The vial was heated to 45° C. for one hour. The reaction was confirmed complete by LC/MS using the methyl ester of the acid in methanol. Volatiles were removed under vacuum until the yellow solid was dry. All material was used as is in the next reaction without further characterization. In a 50 mL vial with a screw-top septum, 1-(5-bromo-3-fluoropyridin-2-yl)-1,2,3,6-tetrahydropyridine-4-carbonyl chloride (28) was dissolved in 10 mL tetrahydrofuran (THF), stirred with a magnetic stir bar, and cooled to 0° C. 1.1 eq. 2-amino-6-fluorobenzothiazole (3.65 mMol) were dissolved in 2 mL dimethylformamide (DMF) and the solution slowly added to the vial. After the reaction stirred for 10 minutes, 3 eq. pyridine (9.96 mMol) were added to the mixture dropwise and the reaction progressed for 18 hours. The precipitate was collected by vacuum filtration and washed with 2×15 mL EtOAc. (30% white solid): m/z 451, 1H NMR (DMSO) δ 12.43 (s, 1H), 8.17-8.10 (m, 1H), 7.96-7.95 (m, 1H), 7.86-7.78 (m, 1H), 7.71-7.64 (m, 1H), 7.28-7.19 (m, 1H), 7.09-7.04 (m, 1H), 4.19-4.12 (m, 2H), 3.64-3.51 (m, 2H), 2.59-2.53 (m, 2H).

Provenance & Evidence