Sulfuric Acid → 4-Hydroxymethylpyrazolo[1,5-a]pyridine-2-carboxylic acid

HRID 2039771Notes

Reaction equation

[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][OH:8])[CH:2]=1.C1(C)C=C(C)C=C(C)C=1S(O[NH2:21])(=O)=O.C[O:24][C:25]([C:27]#[C:28]C(OC)=O)=[O:26].OS(O)(=O)=O>>[OH:8][CH2:7][C:3]1[C:2]2[N:1]([N:21]=[C:27]([C:25]([OH:24])=[O:26])[CH:28]=2)[CH:6]=[CH:5][CH:4]=1

Participants

Reactant 4

HCID 1118Sulfuric Acid

HCID 75103-Pyridinemethanol

HCID 12980Dimethyl acetylenedicarboxylate

HCID 11830845O-(2,4,6-Trimethylbenzenesulfonyl)hydroxylamine

Product 1

HCID 671135914-Hydroxymethylpyrazolo[1,5-a]pyridine-2-carboxylic acid

Procedure

In Scheme I, dicarboxylic acid dimethyl ester 1 is prepared by reaction of the 3-pyridylcarbinol analogue with O-mesitylenesulfonylhydroxylamine in the presence of acetylene dicarboxylic acid dimethyl ester. Reaction of 1 with aqueous H2SO4 affords the 4-hydroxymethylpyrazolo[1,5-a]pyridine-2-carboxylic acid analogue, which is converted to the ethyl ester 2 by reaction with acetyl chloride in absolute ethanol. Oxidation of 2 with Jones reagent yields carboxylic acid 3, which is converted to amide 4 by reaction with an appropriate amine in the presence of BOP.

Sources & evidence

ORD record: ord-0b4d680da5b545f9b05a3045a08e3d37
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580812B2

Reaction notes

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