Trifluoroacetic acid → Benzamide

Participants

Reaction Steps

Stir a solution of 4-[1,2,3]thiadiazol-4-yl-benzoic acid (21 mg, 0.10 mmol) and CDI (19 mg, 0.11 mmol) in DMF (3 mL) at rt for 1.5 h. To the clear solution add 3-aminomethyl-N—[(S)-6-(2,2,2-trifluoro-acetylamino)-4,5,6,7-tetrahydro-benzothiazol-2-yl]-benzamide hydrochloride (45 mg, 0.10 mmol) followed by Et3N (0.098 mL, 0.70 mmol). Stir the mixture at rt overnight. Concentrate and use the mixture in the next step without any purification. Dissolve the crude trifluoroacetamide (50 mg, 0.085 mmol) in 4:1 MeOH/H2O (10 mL). Add potassium carbonate (47 mg, 0.34 mmol) to the mixture and stir at 50° C. for 48 h. Add a small amount of TFA to the mixture and purify by prep-HPLC (10% to 100%, CH3CN/H2O) to give the desired product N—((S)-6-amino-4,5,6,7-tetrahydro-benzothiazol-2-yl)-3-(4-[1,2,3]thiadiazol-4-yl)-aminomethyl)-benzamide in 48% yield (20 mg, 0.041 mmol) MS, electrospray 491.1 (M+H), rt 0.55 min.

Provenance & Evidence