2-(Ethoxymethylene)propanedinitrile → 5-amino-1-(2,5-dimethylphenyl)-1H-pyrazole-4-carbonitrile

Participants

Reaction Conditions

Reaction Steps

2,5-Dimethylphenylhydrazine hydrochloride (CAS no. 56737-78-1) (10 g, 57.92 mmol) was partitioned between EtOAc (100 mL) and NaOH (2M, aq) (60 mL). The organic layer separated and washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated to afford free base of the starting material. The resultant oil was suspended in MeOH (100 mL) under nitrogen at −5° C. 2-(ethoxymethylene)malononitrile (7.07 g, 57.92 mmol) added portionwise over 5 mins and the mixture stirred at ˜0° C. for 30 mins. The reaction mixture was allowed to warm to room temperature and then heated at reflux under nitrogen for 2 hours. The reaction mixture was allowed to cool and evaporated to dryness to afford the product (11.07 g, 90%) which was used without purification. 1H NMR (400 MHz, DMSO) δ 1.98 (3H, s), 2.31 (3H, s), 6.39 (2H, s), 7.07 (1H, s), 7.21-7.28 (2H, m), 7.72 (1H, s); m/z (ES+) (M+H)+=213; HPLC tR=1.79 min.

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