3-chloro-1-(pyridin-3-yl)-1H-pyrazole-5-carboxylic acid → 3-(3-chloro-1H-pyrazol-1-yl)pyridine

HRID 512703

Reaction equation

HRID 512703 reaction equation
[Cl:1][C:2]1[CH:6]=[C:5](C(O)=O)[N:4]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[N:3]=1>[Cu]=O.CN(C)C=O>[Cl:1][C:2]1[CH:6]=[CH:5][N:4]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[N:3]=1

Participants

4

Reactant 1

HCID 917544803-chloro-1-(pyridin-3-yl)-1H-pyrazole-5-carboxylic acid

Product 1

HCID 674995403-(3-chloro-1H-pyrazol-1-yl)pyridine

Reagents, catalysts & solvents 2

HCID 14829Copper oxideCatalystHCID 6228DimethylformamideSolvent

Procedure

In step d of Scheme 2, 3-chloro-1-(pyridin-3-yl)-1H-pyrazole-5-carboxylic acid (6e) is decarboxylated in the presence of copper (II) oxide in polar solvents such as N,N-dimethylformamide at temperatures from about 80° C. to about 140° C. to yield 3-(3-chloro-1H-pyrazol-1-yl)pyridine (5b). It was surprisingly discovered that this decarboxylation only occurs in the presence of copper (II) oxide. Several known decarboxylation agents from the literature such as, for example, hydrochloric acid (See alternate synthetic route, Example 14), sulfuric acid, and palladium (II) trifluoroacetate/trifluoroacetic acid (Pd(TFA)2/TFA) (See “CE-5”) did not yield the desired product.

Sources & evidence

ORD record
ord-81add921e86f4a4eb16a79c65178b312
Source dataset
uspto-grants-2015_08
Patent number
US09102654B2

Linked notes

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