Ammonia → HCID 59332610, compound

Participants

Reaction Conditions

Reaction Steps

5-Bromo-3-[2-(1-methylethyl)-1,1-dioxidotetrahydro-2H-thiopyran-4-yl]-1H-indole-7-carboxylic acid (1.12 g, 2.69 mmol) was dissolved in N,N-Dimethylformamide (DMF) (4 mL). HOBt (1-hydroxybenzotriazole) (0.364 g, 2.69 mmol) and EDC (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide) (1.445 g, 7.54 mmol) were added. The mixture was stirred and a solution of 0.5 N ammonia in dioxane (16.15 mL, 8.07 mmol) was added. The reaction mixture was heated under microwave at 100° C. for 20 minutes. The reaction was diluted with saturated aqueous sodium bicarbonate (30 mL) and extracted with ethyl acetate (3×50 mL). The organic layers were combined, washed with water, dried (MgSO4) and the solvent was removed in vacuo to afford 1.5 g of brown oil. The oil was purified by Flash Chromatography (hexanes/ethyl acetate) to afford a pure fraction of a yellow pure solid (190 mg). The remaining product was recovered from the column as a mixture and was purified by dissolution in ethyl acetate, and sonicating to precipitate 420 mg of white crystals. Both the 190 mg from chromatography and 420 mg from the crystallization are combined to afford 610 mg of the title compound, which was >90% of a single isomer based on LC/MS and 1H NMR. The stereochemistry of the major isomer was assigned as trans based on a series of NOE experiments. The filtrate from the crystallization step above was concentrated to afford 37 mg of mostly the minor (cis) isomer, (racemic)-5-bromo-3-[cis-2-(1-methylethyl)-1,1-dioxidotetrahydro-2H-thiopyran-4-yl]-1H-indole-7-carboxamide.

Provenance & Evidence