反应详情

温度

-78 °C

To a solution (0.2 M) of 1,3-thiazole-5-carboxylic acid (from Combi-blocks) in dry THF a solution of BuLi (1.6 M solution in hexane, 2.2 eq.) was added dropwise at −78° C. and stirred at −78° C. for 45 min. A solution (1 M) of N-methyl-N-methoxytrifluoroacetamide (1.5 eq.) in dry THF was added at −78° C. to the reaction mixture and stirred for 1 h at −60° C. The reaction mixture was quenched by adding NH4Cl solution, then extracted with DCM. The combined organic layer was washed with brine and dried. Evaporation of the solvent gave a residue (LC-MS (ES+) C6H2F3NO3S requires: 225, found: 226 (M+H)+. Retention time: 2.26 min) that was dissolved in DMF. To the resulting solution (0.5 M), HOBt (1.5 eq.) and EDCI (1.5 eq.) were added and stirring was continued for 1 h. N-benzylmethylamine (1.5 eq.) was added and the reaction mixture was stirred at RT O/N. The crude was purified by RP-HPLC to yield (3%) the title compound as a solid.

1. stirringstirred for 1 h at −60° C
2. customThe reaction mixture was quenched
3. additionby adding NH4Cl solution
4. extractionextracted with DCM
5. washThe combined organic layer was washed with brine
6. customdried
7. customEvaporation of the solvent
8. customgave a residue (LC-MS (ES+) C6H2F3NO3S requires: 225, found: 226 (M+H)+. Retention time: 2.26 min) that
9. stirringstirring
10. waitwas continued for 1 h
11. stirringthe reaction mixture was stirred at RT O/N
12. customThe crude was purified by RP-HPLC