反应详情

温度

50 °C

A solution of 5-chloro-N-[4-(methyloxy)-1H-indazol-3-yl]-N-({[2-(trimethylsilyl)ethyl]oxy}methyl)-2-thiophenesulfonamide (Intermediate 8) (150 mg, 0.32 mmol) was treated with 4-(chloromethyl)-N,N-diethylbenzamide (86 mg, 0.38 mmol) and potassium hydroxide (21.3 mg, 0.38 mmol), and the mixture was heated to 50° C. overnight. Reaction mixture was partitioned between DCM (3 mL) and water (3 mL). The organic phase was separated and the aqueous layer was further extracted with 2 mL of DCM. The combined organic solutions were dried (hydrophobic frit) and concentrated under a nitrogen stream in a blowdown unit. The residue was purified by chromatography using a Flash Master system (Solo machine), on a 50 g silica cartridge, eluting with 0 to 100% A in B, A being a 20% EtOAC in DCM solution and B being neat DCM over 60 min. Evaporation of the appropriate fractions gave the title compound (125 mg, 60%) LCMS (System A) RT=1.52 min, ES+ve m/z 680/682(M+NH4)+.

1. customReaction mixture
2. customwas partitioned between DCM (3 mL) and water (3 mL)
3. customThe organic phase was separated
4. extractionthe aqueous layer was further extracted with 2 mL of DCM
5. customThe combined organic solutions were dried (hydrophobic frit)
6. concentrationconcentrated under a nitrogen stream in a blowdown unit
7. customThe residue was purified by chromatography
8. washon a 50 g silica cartridge, eluting with 0 to 100% A in B
9. customover 60 min
10. customEvaporation of the appropriate fractions