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

HRID 718847Notes

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

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).

Workup

temperatureAfter about 10 min the mixture was warmed in an oil bath
temperatureto cool
customThe solvent was removed under reduced pressure
stirringthe material was stirred with water (300 mL)
filtrationAfter about 30 min the solids were collected by filtration
washwashed with water (3×100 mL)
customdried under vacuum at about 65° C.

Sources & evidence

ORD record: ord-3233b010ab2846499bfb6873ab1ce0d5
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193744B2

Reaction notes

Loading…