Hydrochloric Acid → ethyl 5-amino-3-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxylate

HRID 1748429Notes

Reaction equation

HRID 1748429 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[CH:4]=[CH:5][C:6]([NH:9][NH2:10])=[N:7][CH:8]=1.[C:13]([C:15](=[C:21](OCC)[CH3:22])[C:16]([O:18][CH2:19][CH3:20])=[O:17])#[N:14].C(O)C.Cl>O>[NH2:14][C:13]1[N:9]([C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:11])[F:12])=[CH:8][N:7]=2)[N:10]=[C:21]([CH3:22])[C:15]=1[C:16]([O:18][CH2:19][CH3:20])=[O:17]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 46635Ethyl 2-cyano-3-ethoxy-2-butenoateHCID 14776422-Hydrazinyl-5-(trifluoromethyl)pyridine

Product 1

HCID 86692405ethyl 5-amino-3-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxylateYield 54.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

5-(Trifluoromethyl)pyridin-2-ylhydrazine (10.0 g) described in Reference Example 8 and ethyl 2-cyano-3-ethoxy-3-methylacrylate (10.3 g) were added to a mixed solvent of ethanol (40 ml) and 1N hydrochloric acid aqueous solution (40 ml), and the mixture was stirred at reflux temperature for three hours. Water was added to the reaction solution to give ethyl 5-amino-3-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxylate (9.6 g). Next, the compound was added to tetrahydrofuran (50 ml), isoamyl nitrite (20 g) was added and the mixture was stirred at reflux temperature for five hours. The reaction solution was concentrated, a mixed solvent of ethanol (40 ml) and water (40 ml) and sodium hydroxide (5 g) were added and the mixture was stirred at reflux temperature for two hours. Ethanol was evaporated, diluted hydrochloric acid was added and the precipitated solid was recrystallized from aqueous methanol to give the titled compound.

Workup

  1. temperatureat reflux temperature for three hours

Sources & evidence

ORD record
ord-f5c504daa7a645d79df7569f884a840a
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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