2-(Ethoxymethylene)propanedinitrile → 5-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carbonitrile
Reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][NH2:10])=[CH:5][CH:4]=1.C(O[CH:14]=[C:15]([C:18]#[N:19])[C:16]#[N:17])C>CCO>[NH2:19][C:18]1[N:9]([C:6]2[CH:7]=[CH:8][C:3]([F:2])=[CH:4][CH:5]=2)[N:10]=[CH:14][C:15]=1[C:16]#[N:17]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
A flask was charged with (4-fluorophenyl)hydrazine hydrochloride (50.9 g, 313 mmol), EtOH (320 mL) and 2-(ethoxymethylene)malononitrile (40.1 g, 329 mmol). The stirred suspension was treated with TEA (45.8 mL, 329 mmol). After about 10 min the mixture was warmed in an oil bath heated to about 80° C. for about 1.5 h. The mixture was allowed to cool and stir overnight at rt. The solvent was removed under reduced pressure then the material was stirred with water (300 mL). After about 30 min the solids were collected by filtration, washed with water (3×100 mL) and dried under vacuum at about 65° C. to yield 5-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carbonitrile (110, R1=4-Fluorophenyl) (56.2 g, 89%); LC/MS, method 3, Rt=1.64 min, MS m/z 201 (M−H)—. 1H NMR (400 MHz, DMSO) δ 7.77 (s, 1H), 7.59-7.45 (m, 2H), 7.43-7.27 (m, 2H), 6.68 (s, 2H).