反应详情

4-(4-methylpiperazin-1-yl)-2-[{cis-4-[(phenylcarbonyl)oxy]cyclohexyl}(trifluoroacetyl)amino]benzoic acid hydrochloride (1.03 gr, 1.94 mmol) and oxalyl chloride (3.88 mmol) were stirred in DCM dry (20 mL) and a few drops of dry DMF at 0° C., temperature was allowed to reach room temperature in 2 hours. Volatiles were evaporated and the residue dissolved in dry pyridine (25 mL) at 0° C. A solution of 5-(3,5-difluoro-benzyl)-1H-indazol-3-ylamine (387 mg, 1.49 mmol) in dry pyridine (6 mL) was added to the cooled reaction mixture. Temperature was allowed to reach room temperature overnight. Reaction was quenched with NaHCO3 sat. sol and extracted with ethyl acetate. Collected organic phases were dried over Na2SO4, filtered and evaporated to dryness. Residue was purified by column chromatography over silica gel (DCM/AcOEt/EtOH=100/10/15). The so obtained derivative, was dissolved in MeOH (200 mL) and water (20 mL) and treated at 60° C. with LiOH hydrate (160 mg, 3.8 mmol) for 4 hours. MeOH was evaporated and the resulting aqueous phase was extracted with EtOAc. Collected organic phases were dried over Na2SO4, filtered and evaporated to dryness. Residue was purified by column chromatography over silica gel (DCM/EtOH/NH3 5N in MeOH=100/10/2) affording 233 mg of title compound.

1. dry with materialdry (20 mL) and a few drops of dry DMF at 0° C.
2. customVolatiles were evaporated
3. dissolutionthe residue dissolved in dry pyridine (25 mL) at 0° C
4. waitto reach room temperature overnight
5. customReaction
6. customwas quenched with NaHCO3 sat. sol
7. extractionextracted with ethyl acetate
8. dry with materialCollected organic phases were dried over Na2SO4
9. filtrationfiltered
10. customevaporated to dryness
11. customResidue was purified by column chromatography over silica gel (DCM/AcOEt/EtOH=100/10/15)
12. customThe so obtained derivative
13. customMeOH was evaporated
14. extractionthe resulting aqueous phase was extracted with EtOAc
15. dry with materialCollected organic phases were dried over Na2SO4
16. filtrationfiltered
17. customevaporated to dryness
18. customResidue was purified by column chromatography over silica gel (DCM/EtOH/NH3 5N in MeOH=100/10/2)