反应详情

Diisoproylcarbodiimide (0.028 mL, 0.178 mmol) was added to a solution of 2-(4-(tert-butoxycarbonyl)-2-((pyridin-3-yloxy)methyl)piperazin-1-yl)thiazole-4-carboxylic acid (68 mg, 0.162 mmol), morpholine (16 mg, 0.178 mmol), diisopropylethylamine (0.031 mL, 0.178 mmol), and N-hydroxybenzotriazole (24 mg, 0.178 mmol) in CH2Cl2 (2 mL). After stirring overnight, little reaction had taken place. TBTU (0.162 mmol) was added, and stirring was continued at rt for 4 h. The reaction mixture was quenched with 1 N NaOH (2 mL) and stirred for 1 h. The reaction mixture was diluted with EtOAc (20 mL) and was washed with 1 N NaOH (2×10 mL) and brine (10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified by column chromatography (50 to 100% EtOAc in hexanes gradient), yielding 35.4 mg (45%) of the title compound. LC-MS: RT=6.77 min, [M+H]+=490.9. Rf=0.07 in 100% EtOAc.

1. customlittle reaction
2. stirringstirring
3. waitwas continued at rt for 4 h
4. customThe reaction mixture was quenched with 1 N NaOH (2 mL)
5. stirringstirred for 1 h
6. additionThe reaction mixture was diluted with EtOAc (20 mL)
7. washwas washed with 1 N NaOH (2×10 mL) and brine (10 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe material was purified by column chromatography (50 to 100% EtOAc in hexanes gradient)