2-(Ethoxymethylene)propanedinitrile → 5-amino-1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazole-4-carbonitrile

HRID 31379

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:12][NH2:13].C(O[CH:17]=[C:18]([C:21]#[N:22])[C:19]#[N:20])C>CO>[NH2:22][C:21]1[N:12]([C:3]2[CH:4]=[CH:5][C:6]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:7][C:2]=2[F:1])[N:13]=[CH:17][C:18]=1[C:19]#[N:20]

Participants

Conditions

Temperature: -6 °C

Procedure

To a stirred suspension of 2-fluoro-4-methylsulfonylphenyl hydrazine (1) (4.0336 Kg; 1 eq) (commercially available from, e.g., Peakdale Molecular, Ltd.) in methanol (12.7723 Kg) was added a suspension of ethoxymethylene malononitrile (2.6564 Kg, 1.101 equivalents) in methanol (11.212 Kg) at a rate sufficiently slow to maintain the reaction mixture at −10° to 0° C. with reactor jacket cooling. After the addition had been completed, the reaction mixture was stirred for 1 hour at −6° C. and then heated to reflux for 5 hours, at which time the reaction mixture gave a pyrazole (3): hydrazine (1) HPLC peak area ratio of 105:1. Solvent (20.5153 Kg) was then distilled off the reaction mixture at atmospheric pressure, leaving a residue having less than 20% of the original volume. The resulting mixture was used directly in the next step.

Workup

temperatureto maintain the reaction mixture at −10° to 0° C. with reactor jacket
temperaturecooling
additionAfter the addition
temperatureheated
temperatureto reflux for 5 hours, at which time the reaction mixture

Sources & evidence

ORD record: ord-2cf28deae1a344dd9efb094b5ca7a968
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07425630B2

Linked notes

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