p-Toluenesulfonic acid → ethyl 2-(4-(4-chloro-2-methylphenyl)-1,3,7-trimethyl-4,6-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)acetate

Participants

Reaction Conditions

Reaction Steps

To a solution of 1,3-dimethyl-1H-pyrazol-5-amine (0.58 g, 5.22 mmol, Oakwood Chemicals), 4-chloro-2-methylbenzaldehyde (0.81 g, 5.22 mmol, Ark Pharm) and p-TSA (0.10 g, 0.52 mmol) in acetonitrile (10.5 mL) was added ethyl 3-mercapto-4-oxopentanoate (1.74 g, 9.87 mmol) and stirred at about 90° C. for about 18 h. The reaction mixture was cooled to ambient temperature and saturated NaHCO3 (15 mL) and DCM (20 mL) were added. The organic layer was separated and the aqueous layer was back extracted using DCM (20 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (SiO2, EtOAc/heptane 100:0 to 0:50) to afford ethyl 2-(4-(4-chloro-2-methylphenyl)-1,3,7-trimethyl-4,6-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)acetate (0.85 g, 1.97 mmol, 37%). LC-MS (Table 1, Method g) Rt=2.66, 2.63 min, m/z 406 (M+H)+.

Provenance & Evidence