5-Amino-1-(4-fluorophenyl)-1H-pyrazole-4-carbonitrile

Sodium hydride as a 60percent dispersion in mineral oil (5.90 g, 1.2 eq, 0.147 mol.) was added slowly to ethanol (200 ml) at room temperature. To the solution of sodium ethoxide in ethanol was added 4-fluorophenylhydrazine hydrochloride (23.96 g, 1.2 eq, 0.147 mol.), addition of ethoxymethylene malonitrile (15.00 g, 1.0 eq, 0.123 mol.) shortly followed. The reaction mixture was heated to reflux with stirring for 2 hours. The reaction was then allowed to cool to room temperature, once at room temperature diethyl ether (50 ml) was added to the reaction mixture. The resultant precipitate was collected by filtration, washed with diethyl ether (2 x 100 ml) and dried in vacuo to give the title compound as a beige solid (21.5 g, 0.106 mol, 86percent). LCMS: [M+H]Example 5A8.7 g (53.5 mmol) of 4-fluorphenylhydrazine hydrochloride was suspended with 6.5 g (53.5 mmol) of ethoxymethylenemalononithle in 13 ml of ethanol, and 22.2 ml (160 mmol) of thethylamine were added. The reaction mixture was heated to 50General procedure: A mixture of the appropriate phenylhydrazine (0.001 mol)and 10 mL of ethanol was stirred and allowed to reflux.Then, 2-(ethoxymethylene)malononitrile (0.001 mol) dissolvedin 10 mL of ethanol was slowly added. The reactionmixture was refluxed for 2 h. The reaction mixture waspoured into 50 mL of ice-cold water. The precipitate wascollected by filtration and washed with water to provide10a–c in 61–80percent yield.5-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carbonitrile (10a)Yield: 61percent. MP: 173–174 °C. IR (cm−1): 3297–3183; 2225;1662; 1568; 1222. 1H NMR (400 MHz, DMSO-d6, TMS, δin p.p.m.): 7.31–7.25; (m; 2 H; H3′, H5′); 7.54–7.49; (m;2H; H2′, H6′); 7.67; (s; 1 H; H3). 13C NMR (100 MHz, DMSO-d6, TMS, δ in ppm): 73.2 (C4); 114.8 (CN); 116.3(d; J = 22.8 Hz; C3′, C5′); 126.9 (d; J = 8.9 Hz; C2′, C6′);133.7 (d; J = 2.8 Hz; C1′) 141.7 (C5); 151.4 (C3); 161.2 (d;J = 243.6 Hz; C4′). 19F NMR (376 MHz, DMSO-d6, TMS, δin p.p.m.): -114.26. EI [M + 1]+ 203.07.2-(Methoxymethylene)malononitrile (1.00 g, 8.19 mmol), (4-fluorophenyl) hydrazine hydrochloride (1.40 g, 8.61 mmol), triethylamine (1.66 g, 16.4 mmol) and ethanol (50 mE) were added to a 100-mE round-bottom flask fitted with a magnetic stir bar and condenser. The resulting solution was heated at reflux for 16 h. The resulting mixture was concentrated under vacuum. The residue was purified by colunm chromatography eluting with dichloromethane/ methanol (10:1 v/v)to give 5-amino-i-(4-fluorophenyl)-1H- pyrazole-4-carbonitrile (1.00 g, 60percent). ECMS: (ESI) mlz 203 [M+H].

Molecular Weight:202.19
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:202.06547440
Monoisotopic Mass:202.06547440
Topological Polar Surface Area:67.6
Heavy Atom Count:15
Complexity:266
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes