反应详情

Dissolve 3-[5-(4-cyano-phenyl)-[1,3,4]-thiadiazol-2-ylmethyl]-benzoic acid (0.13 g, 0.28 mmol) in 3 mL of dimethylacetamide. Add N,N-diisopropylethyl amine (0.17 mL, 0.95 mmol), of 7-aza-hydroxybenzotriazole (0.05 g, 0.37 mmol) and EDC (0.07, (0.36 mmol). Stir the mixture at room temperature for 1 h and add (S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-ylamine dihydrobromide (0.14 g, 0.35 mmol) in one portion. Heat the mixture at 60° C. for 15 h. Cool to room temperature and dilute with H2O. Add a saturated aqueous solution of sodium bicarbonate until the pH of the solution is alkaline causing a solid to precipitate from solution. Collect the solid by filtration, wash with H2O and dry on the filter pad. Purify the material by preparative reverse phase HPLC (CH3CN:H2O with 0.1% trifluoroacetic acid) to give 0.025 g, 14% yield of 3-[5-(4-cyano-phenyl)-[1,3,4]thiadiazol-2-ylmethyl]-N—((S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-yl)-benzamide as a solid. MS, ES+ 543.62 (M+H), rt 1.50 min.

1. temperatureHeat the mixture at 60° C. for 15 h
2. temperatureCool to room temperature
3. customto precipitate from solution
4. customCollect the solid
5. filtrationby filtration
6. washwash with H2O
7. customdry on the filter pad
8. customPurify the material by preparative reverse phase HPLC (CH3CN:H2O with 0.1% trifluoroacetic acid)