Diisopropylethylamine → 7-[(3,4-Difluoro-2-methylphenyl)carbonyl]-3-(1,2,4-thiadiazol-5-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

Participants

Reaction Steps

3,4-Difluoro-2-methylbenzoic acid (I68)(124 mg, 0.720 mmol) was dissolved in dry N,N-dimethylformamide (DMF) (4.7 mL) before treating with HATU (274 mg, 0.720 mmol) and DIPEA (0.252 mL, 1.441 mmol) and stirring for 15 mins at RT, under argon before adding 3-(1,2,4-thiadiazol-5-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine (I115)(100 mg, 0.480 mmol) and stirring for a further 18 hours. LCMS confirmed that the desired material was present and that no start material was left. The reaction was worked up by diluting with DCM (50 ml), washing with water (50 ml). The aqueous layer was extracted with DCM (2×30 ml). The combined extracts were washed with brine (30 ml), dried (Na2SO4), filtered and evaporated to afford a pale pink gum. The product was purified on a SNAP 50 g cartridge, eluting with 0-10% MeOH in DCM, the desired fractions were collected and the solvent was evaporated to afford a dark orange gum. Due to presence of residual DMF the crude gum product was diluted with DCM (30 ml), washed with brine (2×20 ml), dried (Na2SO4), filtered and evaporated to afford an orange foam. The foam triturated with n-hexane to afford a pale orange solid. Liquers were removed and the residue was triturated again with n-Hexane. Liquers were removed and the solid was dried overnight in the vac oven at 40° C. to afford desired product in 146 mg as a pale orange solid.

Provenance & Evidence