p-Toluenesulfonic acid monohydrate → (S)-3-(4-(6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

(S)—N′-(6-Chloropyridazin-3-yl)-4-(5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)benzohydrazide (100 mg, 0.228 mmol) was dissolved in MeOH (2.284 mL). To the reaction mixture was added 4-methylbenzenesulfonic acid hydrate (43.4 mg, 0.228 mmol, commercially available from Sigma-Aldrich, Milwaukee, Wis.). The mixture was heated at 55° C. and was stirred overnight. LC-MS indicated incomplete conversion. The mixture was then heated at 100° C. in a microwave for 1 hour. LC-MS indicated complete and clean conversion to the desired product. The reaction mixture was then concentrated under reduced pressure and providing a yellow residue. The residue was dissolved in 2 mL of MeOH and 1 mL of NH4OH, and the mixture was purified by reverse-phase preparative HPLC using 0.1% TFA in ACN/H2O, gradient 20% to 90% over 20 minutes. The pure fractions were combined and diluted with 30% ammonium hydroxide, and the aqueous layer was extracted with DCM (3×20 mL) to provide (S)-3-(4-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (30 mg, 0.071 mmol, 31.3% yield) as a yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 8.50 (d, J=9.40 Hz, 1H), 8.20 (d, J=8.33 Hz, 2H), 7.74 (d, J=9.19 Hz, 2H), 7.52 (d, J=9.62 Hz, 1H), 7.36-7.42 (m, 2H), 7.26-7.35 (m, 3H), 5.55 (s, 1H), 1.67 (s, 3H), 0.94 (s, 3H). m/z (ESI) 420.0 (M+H)+.

Provenance & Evidence