4-[(3-Chloro-2-methylphenyl)carbonyl]-2-piperazinone (I131)(250 mg, 0.989 mmol) was suspended in dry Dichloromethane (DCM) (3 mL) before treating with trimethyloxonium tetrafluoroborate (185 mg, 1.187 mmol) and stirring for 16 hours at RT under argon before adding 5-methyl-1,3-thiazole-4-carbohydrazide (I123) (233 mg, 1.484 mmol) and stirring for a further 3 hours. DCM was removed by evaporation and the residue was dissolved in 1-butanol (3.00 mL) before heating at 110° C. for 4 hours then cooled to RT overnight. The reaction was worked up by diluting with DCM (50 ml) and washing with saturated sodium bicarbonate solution (50 ml). The aqueous layer was extracted with DCM (2×30 ml), the combined extracts were washed with brine (30 ml), dried (MgSO4), filtered and evaporated to afford a pale yellow cloudy gum as crude product. The product was purified on 50 g Isolera column, eluting with DCM (3CV) then 0-10% MeOH/DCM over 10CV. The desired fractions were isolated, the solvent evaporated and the residue was further purified by MDAP (formic acid method). The desired fraction was identified and the solvent evaporated to afford a white foam of desired product in 130 mg.
