Phosphorus oxybromide → HCID 178468567, compound

HRID 2360696Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15]([CH3:16])=[N:14][NH:13][C:8]=2[N:9]=[C:10](O)[CH:11]=1)=[O:5])[CH3:2].P(Br)(Br)([Br:19])=O.C([O-])(=O)C.[K+]>C1(C)C=CC=CC=1.O>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15]([CH3:16])=[N:14][NH:13][C:8]=2[N:9]=[C:10]([Br:19])[CH:11]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 6-hydroxy-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (13.7 g) and phosphorous oxybromide (19.5 g) in toluene (300 mL) was stirred at 110° C. for 5 h, cooled to r.t., and added dropwise into an ice cold solution of potassium acetate (18.2 g) in water (300 mL). The mixture was extracted twice with ethyl acetate, the combined organic phases were washed with brine, dried over magnesium sulfate and concentrated in vacuo. 6-Bromo-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (4.6 g, 26%) were obtained. This material was dissolved in THF (60 mL), and 3,4-dihydro-2H-pyran (1.6 mL) and p-toluenesulfonic acid monohydrate (0.91 g) were added. The solution was stirred at r.t. for 48 h, then 3,4-dihydro-2H-pyran (1.6 mL) were added and the solution stirred again for 48 h. The mixture was poured into water and extracted with ethyl acetate, the organic layer was dried over magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (silica, heptane/ethyl acetate gradient). 2.2 g (38%) of the title compound were obtained.

Workup

temperaturecooled to r.t.
extractionThe mixture was extracted twice with ethyl acetate
washthe combined organic phases were washed with brine
dry with materialdried over magnesium sulfate
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-fa660d363c3a4b2f90ea05e41348d802
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08686150B2

Reaction notes

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