反应详情

温度

80 °C

To a stirred solution of 2-(pyrrolidine-1-yl)ethanol (0.102 mL, 0.872 mmol) in dry tetrahydrofuran (20 mL) was added sodium hydride (70 mg, 1.771 mmol) at 0° C. The reaction mixture was heated to 80° C. After 10 min, ethyl 4-(5-chloropyrazin-2-yl)-2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-1,3-thiazole-5-carboxylate (Example 59, 250 mg, 0.436 mmol) was added to the reaction mixture at 80° C. and further maintained at 80° C. for 10 min. After the completion of the reaction, the reaction mixture was cooled and carefully quenched by adding ice pieces. The aqueous layer was extracted with ethyl acetate (2×50 mL) to get rid of any organic impurities and discarded. The aqueous layer was acidified to pH=2 using 2N HCl solution and was extracted with 10% methanol/dichloromethane (2×100 mL). The organic layer was dried and concentrated under reduced pressure to yield the product. The obtained product was stirred in acetonitrile (10 mL). The solid was filtered and dried to obtain 120 mg (45%) of 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-{5-[2-(pyrrolidin-1-yl)ethoxy]pyrazin-2-yl}-1,3-thiazole-5-carboxylic acid as yellow solid.

1. temperaturefurther maintained at 80° C. for 10 min
2. customAfter the completion of the reaction
3. temperaturethe reaction mixture was cooled
4. customcarefully quenched
5. additionby adding ice pieces
6. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
7. customto get rid of any organic impurities
8. extractionwas extracted with 10% methanol/dichloromethane (2×100 mL)
9. customThe organic layer was dried
10. concentrationconcentrated under reduced pressure
11. customto yield the product
12. filtrationThe solid was filtered
13. customdried