Water → 3-amino-5-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile

HRID 2405677Notes

Reaction equation

HRID 2405677 reaction equation
[C:1]([C:3]([C:20]#[N:21])=[C:4](OC)[C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:7][CH:6]=1)#[N:2].O.[NH2:23][NH2:24].O>C(O)C>[NH2:2][C:1]1[C:3]([C:20]#[N:21])=[C:4]([C:5]2[CH:10]=[CH:9][C:8]([O:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:7][CH:6]=2)[NH:24][N:23]=1

Participants

5

Reactant 3

HCID 962WaterHCID 24654Hydrazine hydrate (1:1)HCID 223472272-((Methoxy)(4-phenoxyphenyl)methylene)malononitrile2×

Product 1

HCID 223467843-amino-5-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

1,1-Dicyano-2-hydroxy-2-(4-phenoxyphenyl)ethene (56.5 g) in acetonitrile (780 mL) and methanol (85 mL) is stirred under nitrogen at 0° C. while adding diisopropylethylamine (52.5 mL) followed by 2M trimethylsilyldiazomethane (150 mL) in THF. The reaction is stirred for 2 days at 20° C., and then 2 g of silica is added (for chromatography). The brown-red solution is evaporated in vacuo, the residue dissolved in ethyl acetate and washed well with water then brine, dried and evaporated. The residue is extracted with diethyl ether (3×250 mL), decanting from insoluble oil. Evaporation of the ether extracts gives 22.5 g of 1,1-dicyano-2-methoxy-2-(4-phenoxyphenyl)ethene as a pale orange solid. The insoluble oil is purified by flash chromatography to give 15.0 g of a red-orange oil. 1,1-Dicyano-2-methoxy-2-(4-phenoxyphenyl)ethene (22.5 g) and 1,1-dicyano-2-methoxy-2-(4-phenoxyphenyl)ethene oil (15 g) are treated with a solution of hydrazine hydrate (18 mL) in ethanol (25 mL) and heated on the steambath for 1 hour. Ethanol (15 mL) is added followed by water (10 mL). The precipitated solid is collected and washed with ethanol:water (4:1) and then dried in air to give 3-amino-4-cyano-5-(4-phenoxyphenyl)pyrazole as a pale orange solid.

Workup

  1. temperatureheated on the steambath for 1 hour
  2. customThe precipitated solid is collected
  3. washwashed with ethanol:water (4:1)
  4. customdried in air

Sources & evidence

ORD record
ord-1804d39c5b474af28d057e1fa25eae6d
Source dataset
uspto-grants-2014_08
Patent number
US08809273B2

Reaction notes

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