(2-Fluorobenzyl)hydrazine → ethyl 5-amino-1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate

HRID 2120563Notes

Reaction equation

HRID 2120563 reaction equation
[C:1]([CH2:3][C:4](=O)[C:5]([O:7][CH2:8][CH3:9])=[O:6])#[N:2].[F:11][C:12]1[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=1[CH2:14][NH:15][NH2:16]>O1CCOCC1>[NH2:2][C:1]1[N:15]([CH2:14][C:13]2[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=2[F:11])[N:16]=[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH:3]=1

Participants

4

Reactant 2

HCID 10374537(2-Fluorobenzyl)hydrazineHCID 11309560Ethyl 3-cyano-2-oxopropanoate

Product 1

HCID 11391384ethyl 5-amino-1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The compound of the formula (II) is obtainable in a multi-stage synthesis from the sodium salts of ethyl cyanopyruvate, which is known from the literature (Borsche and Manteuffel, Liebigs. Ann. Chem. 1934, 512, 97). By reaction thereof with 2-fluorobenzylhydrazine with heating and under a protective gas atmosphere in an inert solvent such as dioxane, ethyl 5-amino-1-(2-fluorobenzyl)pyrazole-3-carboxylate is obtained, which cyclizes by means of reaction with dimethylaminoacrolein in the acidic medium under a protective gas atmosphere and with heating to give the corresponding pyridine derivative. This pyridine derivative, ethyl 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylate, is converted by means of a multi-stage sequence, consisting of conversion of the ester into the corresponding amide using ammonia, dehydration using a dehydrating agent such as trifluoroacetic anhydride to give the corresponding nitrite derivative, reaction of the nitrile derivative with sodium ethoxide and final reaction with ammonium chloride, into the compound of the formula (II).

Workup

  1. customBy reaction

Sources & evidence

ORD record
ord-98993f203a1d4501b26cf6aa687d083e
Source dataset
uspto-grants-2004_02
Patent number
US06693102B2

Reaction notes

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