Dichloromethane → 5-amino-1-(2-bromo-6-chlorophenyl)-1H-pyrazole-4-carbonitrile

Participants

Reaction Steps

(2-Bromo-6-chlorophenyl)hydrazine hydrochloride (Intermediate AH2) (4.71 g, 18.26 mmol) was partitioned between DCM (300 mL) and 2M NaOH (20 mL). Allowed to Stir for 1 hour. The two phases were separated. The organic phase was reduced under vacuum to give the free base. This was dissolved in MeOH (60 mL), and stirred in a cooling bath at 0° C. (Ethoxymethylene)malononitrile (2.230 g, 18.26 mmol) added portionwise. The reaction mixture was then allowed to warm to ambient temperature and stirred for 1 hour. The mixture was then heated to reflux and stirred for 16 hours. Allowed to cool to ambient temperature. The reaction mixture was concentrated to give a solid, which was triturated under MeOH. A solid was filtered off. This was dried to afford the product (4.59 g, 85%). 1H NMR (400 MHz, DMSO) δ 6.79 (2H, s), 7.54-7.47 (1H, m), 7.70 (1H, dd), 7.79 (1H, s), 7.81 (1H, d). m/z (ES+) (M+H)+=299; HPLC tR=1.70 min.

Provenance & Evidence