Sodium Bicarbonate → N-(6-{6-Chloro-5-[(phenylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

DMA (9 ml) was added to a Biotage microwave vial containing N-(6-bromo-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide (175 mg, 0.519 mmol), Pd(dppf)Cl2 (85 mg, 0.104 mmol), potassium acetate (153 mg, 1.56 mmol) and 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (86 mg, 0.338 mmol). The vial was sealed, the solution was degassed with nitrogen, then heated in a Biotage Initiator at 80° C. for 20 mins. Pd(dppf)Cl2 (85 mg, 0.104 mmol) was added to the reaction, the vial was sealed, degassed with nitrogen, then heated in a Biotage Initiator at 80° C. for 20 mins. Pd(PPh3)4 (30 mg, 0.026 mmol), N-(5-bromo-2-chloro-3-pyridinyl)benzenesulfonamide (361 mg, 1.038 mmol) and sodium bicarbonate (0.778 ml, 1.56 mmol) were added to the reaction, which was heated in a Biotage Initiator at 150° C. for 15 mins. Saturated sodium bicarbonate (100 ml) was added and the resulting suspension was washed with ethyl acetate (3×100 ml). Sodium chloride was added to improve separation. The organic layers were filtered through a hydrophobic frit, combined and dried under vacuum. The solid obtained was pre-adsorbed on silica and purified by silica chromatography (100 g cartridge) using 0-15% MeOH in DCM over 60 mins. Appropriate fractions were combined and dried under vacuum. The still crude compound was loaded onto an SPE (50 g) cartridge using DCM and the column was eluted with ethyl acetate:toluene:MeOH (200 ml, 14:5:1, v/v/v). Appropriate fractions were combined and the solvent was evaporated. The material obtained was dissolved in MeOH:DMSO (1 ml, 1:1, v/v) and further purified by HPLC as follows:

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