3,4-dihydro-2H-pyran → 6-chloro-3-iodo-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester

HRID 82023Notes

Reaction equation

HRID 82023 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15]([I:16])=[N:14][NH:13][C:8]=2[N:9]=[C:10]([Cl:12])[CH:11]=1)=[O:5])[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:29]1[CH:34]=[CH:33][CH2:32][CH2:31][CH2:30]1>C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15]([I:16])=[N:14][N:13]([CH:30]3[CH2:31][CH2:32][CH2:33][CH2:34][O:29]3)[C:8]=2[N:9]=[C:10]([Cl:12])[CH:11]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 178468965HCID 178468965, compound

Product 1

HCID 866781586-chloro-3-iodo-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl esterYield 54.2%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of 6-chloro-3-iodo-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (14 g, 39.8 mmol) and p-toluenesulfonic acid monohydrate (0.75 g, 3.9 mmol) in anhydrous chloroform (200 ml) at 0° C. was added dropwise 3,4-dihydro-2H-pyran (5.45 ml, 59.7 mmol). The reaction mixture was allowed to warm to room temperature, stirred overnight and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography using a stepwise gradient of ethyl acetate (0-20%) in cyclohexane to afford the title compound as a yellow solid (9.4 g, 54%). LC/MS (Method LC8): Rt=2.08 min; m/z=351 [M+H-THP]+.

Workup

  1. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8b3c2d24794a40659d4e672c3317ebc7
Source dataset
uspto-grants-2014_09
Patent number
US08846712B2

Reaction notes

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