2,6-Lutidine → 5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrile

HRID 2065863Notes

Reaction equation

HRID 2065863 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([Cl:12])[C:3]=1[NH:13][NH2:14].N1C(C)=CC=CC=1C.Cl/[C:24](=[CH:27]/[C:28]#[N:29])/[C:25]#[N:26].Cl/C(=C\C#N)/C#N>CO>[NH2:29][C:28]1[N:13]([C:3]2[C:2]([Cl:1])=[CH:7][C:6]([C:8]([F:9])([F:11])[F:10])=[CH:5][C:4]=2[Cl:12])[N:14]=[C:24]([C:25]#[N:26])[CH:27]=1

Participants

6

Reactant 4

HCID 79372,6-LutidineHCID 688223[2,6-Dichloro-4-(trifluoromethyl)phenyl]hydrazineHCID 6436674CHLOROFUMARONITRILEHCID 6440946(E)-2-Chloro-2-butenedinitrile

Product 1

HCID 33039135-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrileYield 71%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 50 mL round-bottom flask was charged with (2,6-dichloro-4-trifluoromethyl-phenyl)-hydrazine (1.2 g, 4.84 mmol), 2,6-lutidine (0.57 g, 5.32 mmol, 1.1 equiv.) and methanol (10 mL). A mixture of chloromaleonitrile and chlorofumaronitrile (0.82 g, 7.29 mmol) was slowly added at 20-25° C. Stirring was continued for about 16 hours at that temperature. The solution was then concentrated at a pressure of 50 mbar. The residue was purified by flash column chromatography (silica, hexanes/EtOAc 100:0→70:30) to give the product as a off-white solid (1.1 g, 3.43 mmol, 71%), melting point: 117-118° C., 1H-NMR (360 MHz, CDCl3): δ [ppm]=7.78 (d, 2H, J=0.4 Hz); 6.04 (s, 1H); 3.83 (bs, 2H), 13C-NMR (125 MHz, DMSO-d6): δ [ppm]=150.0; 136.0; 135.9; 132.7 (q, J=34 Hz); 126.43; 126.42; 122.4 (q, J=273 Hz); 114.6; 90.8.

Workup

  1. additionwas slowly added at 20-25° C
  2. concentrationThe solution was then concentrated at a pressure of 50 mbar
  3. customThe residue was purified by flash column chromatography (silica, hexanes/EtOAc 100:0→70:30)

Sources & evidence

ORD record
ord-029d9fd27e374112ad9987c7938dfa29
Source dataset
uspto-grants-2012_10
Patent number
US08288563B2

Reaction notes

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