Pyridine → (S)-2-[({[5-Amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]carbonyl}amino)methyl]-3,3,3-trifluoro-2-hydroxypropyl 4-methylbenzenesulfonate

Participants

Reaction Conditions

Reaction Steps

(S)-5-Amino-1-(4-fluorophenyl)-N-[3,3,3-trifluoro-2-hydroxy-2-(hydroxymethyl)propyl]-1H-pyrazole-4-carboxamide (90 mg) was dissolved in dry dichloromethane (3 ml) and dry pyridine (3 ml) and cooled in an ice bath under nitrogen. p-Toluenesulphonyl chloride (62 mg) was added and the reaction was stirred at ice bath temperature for 1 hour and then at room temperature for 24 hours. p-Toluenesulphonyl chloride (25 mg) was added and the reaction was stirred at room temperature, under nitrogen over the weekend. p-Toluenesulphonyl chloride (25 mg) was added and the reaction was stirred at room temperature under nitrogen for 2 hours and heated at 50° C. for 2 hours and left stirring at room temperature overnight. The solvent was evaporated and the residue was partitioned between dichloromethane and water. The organic layer was washed with 1M hydrochloric acid, water, sodium bicarbonate and brine, dried using a hydrophobic frit and evaporated to give a beige foam (94 mg). This was dissolved in dichloromethane and applied to a 10 g SPE cartridge and purified on the Flashmaster eluting with a 0-50% ethyl acetate in cyclohexane over a 20 minute gradient. The appropriate fraction was evaporated to give the title compound as a colourless oil (83 mg).

Provenance & Evidence