4-(chloromethyl)-N,N-diethylbenzamide

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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)+. Reaction mixture was partitioned between DCM (3 mL) and water (3 mL) The organic phase was separated the aqueous layer was further extracted with 2 mL of DCM The combined organic solutions were dried (hydrophobic frit) concentrated under a nitrogen stream in a blowdown unit The residue was purified by chromatography on a 50 g silica cartridge, eluting with 0 to 100% A in B over 60 min Evaporation of the appropriate fractions

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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)+. Reaction mixture was partitioned between DCM (3 mL) and water (3 mL) The organic phase was separated the aqueous layer was further extracted with 2 mL of DCM The combined organic solutions were dried (hydrophobic frit) concentrated under a nitrogen stream in a blowdown unit The residue was purified by chromatography on a 50 g silica cartridge, eluting with 0 to 100% A in B over 60 min Evaporation of the appropriate fractions

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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)+. Reaction mixture was partitioned between DCM (3 mL) and water (3 mL) The organic phase was separated the aqueous layer was further extracted with 2 mL of DCM The combined organic solutions were dried (hydrophobic frit) concentrated under a nitrogen stream in a blowdown unit The residue was purified by chromatography on a 50 g silica cartridge, eluting with 0 to 100% A in B over 60 min Evaporation of the appropriate fractions