反应详情

Prepared as described for 4-hydroxy-6-(2-phenylethyl)pyridazin-3(2H)-one (Example 1) from 3,4-bis(benzyloxy)-6-((3-methyl-4-(trifluoromethyl)phenyl)-ethynyl)pyridazine (Intermediate 74) except THF was used as the solvent. The reaction mixture was filtered through a diatomacious earth cartridge, eluting with further THF and methanol. The filtrate was concentrated under reduced pressure and purified by reverse phase column chromatography (eluting with 5-100% aqueous acetonitrile with acid modifier). The desired fractions were combined and freeze dried to give a pale yellow solid, which was recrystallised from methyl tert-butyl ether to give a white solid. The filtrate was concentrated under reduced pressure, and the filtrate and crystals purified separately by preparative HPLC. The two batches were combined and recrystallised from a mixture of methyl tert-butyl ether and ethyl acetate to afford 4-hydroxy-6-(3-methyl-4-(trifluoromethyl)-phenethyl)pyridazin-3(2H)-one as a white solid (31 mg, 4%).

1. customPrepared
2. filtrationThe reaction mixture was filtered through a diatomacious earth cartridge
3. washeluting with further THF and methanol
4. concentrationThe filtrate was concentrated under reduced pressure
5. custompurified by reverse phase column chromatography (eluting with 5-100% aqueous acetonitrile with acid modifier)
6. customfreeze dried
7. customto give a pale yellow solid, which
8. customwas recrystallised from methyl tert-butyl ether
9. customto give a white solid
10. concentrationThe filtrate was concentrated under reduced pressure
11. customthe filtrate and crystals purified separately by preparative HPLC
12. customrecrystallised from a mixture of methyl tert-butyl ether and ethyl acetate