Potassium Carbonate → 5-[5-(1-Azetidinylsulfonyl)-2-thienyl]-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-7-carboxamide (21 mg, 0.050 mmol), 1-[(5-bromo-2-thienyl)sulfonyl]azetidine (28.3 mg, 0.100 mmol), and K2CO3 (20.81 mg, 0.151 mmol) in 1,4-dioxane (0.22 mL) and water (0.110 mL) was degassed with argon in a Biotage microwave vial for 10 min. PdCl2(dppf) (3.67 mg, 5.02 μmol) was added, the vial was sealed, and the reaction was heated at 100° C. for 5 min in a Biotage microwave at high absorption. Additional PdCl2(dppf) (3.67 mg, 5.02 μmol) was added, and the reaction was heated at 130° C. in a Biotage microwave for 30 min on high absorption. The aqueous layer was removed via pipette, and the reaction mixture was filtered through a Stratosphere PL-Thio MP SPE cartridge (0.5 g), eluting with 1:1 DCM/MeOH (10 mL). The crude product was dissolved in DMSO (1.2 mL) and purified on a Gilson HPLC (XBridge C18 5 mm OBD 19×100 mm preparatory column), eluting at 15 mL/min with a linear gradient running from 20% CH3CN/H2O (0.1% NH4OH) to 70% CH3CN/H2O (0.1% NH4OH) over 18 min. The desired fractions were concentrated under a stream of nitrogen at 50° C., giving 11.9 mg of impure product. The impure product was dissolved in DMSO (1.2 mL) and purified on a Gilson HPLC(YMC C18 S-5 mm/12 nm 50×20 mm preparatory column), eluting at 20 mL/min with a linear gradient running from 20% CH3CN/H2O (0.1% TFA) to 70% CH3CN/H2O (0.1% TFA) over 10 min. The desired fractions were concentrated under a stream of nitrogen at 50° C., giving 6.1 mg (25%) of the title compound.

Provenance & Evidence