反应详情

温度

0 °C

To a solution of 2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)-6-(1,2,3,6-tetrahydropyridin-4-yl)benzo[d]thiazole (60 mg, 0.138 mmol) and triethylamine (0.039 mL, 0.275 mmol) in CH2Cl2 (1.5 mL) at 0° C. was added methyl 4-(chlorosulfonyl)butanoate (41.5 mg, 0.207 mmol). Upon completion of addition, the reaction mixture was stirred at 0° C. for 15 min. At the conclusion of this period, the reaction mixture was allowed to warm to rt, where it stirred for 1 hr. After this time, the reaction mixture was quenched with saturated aq NaHCO3 (3 mL) and then extracted with CH2Cl2 (3×2 mL). The combined organic layers were washed with brine (2 mL), dried (Na2SO4), filtered, and concentrated to yield the crude product. The crude product was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 50% EtOAc) to afford Compound 5B (56 mg, 0.093 mmol, 68% yield). 1H NMR (500 MHz, chloroform-d) ppm 8.21 (2H, br. s.), 7.62-7.66 (2H, m), 7.37-7.42 (1H, m), 6.06-6.10 (1H, m), 5.43-5.51 (1H, m), 4.18-4.29 (2H, m), 4.00-4.06 (2H, m), 3.67-3.82 (4H, m), 3.60 (2H, t, J=5.6 Hz), 3.07-3.14 (2H, m), 2.65-2.72 (2H, m), 2.54 (2H, t, J=7.0 Hz), 2.43 (2H, t, J=7.6 Hz), 2.12-2.26 (4H, m), 1.92-2.05 (2H, m), 1.50-1.65 (3H, m), 0.96 (3H, t, J=7.3 Hz). LC/MS (m/z)=600 (M+H)+.

1. additionUpon completion of addition
2. temperatureto warm to rt
3. stirringwhere it stirred for 1 hr
4. customAfter this time, the reaction mixture was quenched with saturated aq NaHCO3 (3 mL)
5. extractionextracted with CH2Cl2 (3×2 mL)
6. washThe combined organic layers were washed with brine (2 mL)
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customto yield the crude product
11. customThe crude product was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 50% EtOAc)