反应详情

温度

90 °C

2 N aqueous NaOH solution (2 mL) was added to a solution of N-cyclopropyl-3-fluoro-5-[2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-4-{[(8aR)-3-oxotetrahydro[1,3]oxazolo[3,4-a]pyrazin-7(1H)-yl]sulfonyl}-1,2-dihydroisoquinolin-6-yl]-4-methylbenzamide (Example 49d, 0.291 g) in methanol (2 mL) and the mixture stirred at 90° C. for 45 min. The reaction was neutralised with acetic acid and the volatiles removed under reduced pressure before partitioning between water and DCM. The organic layer was separated and the aqueous extracted further (2×) and the combined organics dried (MgSO4), filtered and evaporated. The residue was purified by SCX (eluting with methanol to remove impurities, then flushing with methanolic ammonia to elute product). Further purification by preparative HPLC (Xbridge column using a 95-5% gradient of 0.3% aqueous ammonia in acetonitrile), solvent evaporation under reduced pressure and trituration with diethyl ether gave the title compound (0.059 g).

1. customthe volatiles removed under reduced pressure
2. custombefore partitioning between water and DCM
3. customThe organic layer was separated
4. extractionthe aqueous extracted further (2×)
5. dry with materialthe combined organics dried (MgSO4)
6. filtrationfiltered
7. customevaporated
8. customThe residue was purified by SCX (
9. washeluting with methanol
10. customto remove impurities
11. customflushing with methanolic ammonia
12. washto elute product)
13. customFurther purification by preparative HPLC (Xbridge column
14. customsolvent evaporation under reduced pressure and trituration with diethyl ether