Phosphorus oxybromide → HCID 178468567, compound

HRID 2279086Notes

Reaction equation

HRID 2279086 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

6

Reactant 3

HCID 24613Phosphorus oxybromideHCID 517044Potassium AcetateHCID 178469359HCID 178469359, compound

Product 1

HCID 178468567HCID 178468567, compoundYield 26.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

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 a membrane pump vacuum. 6-Bromo-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (4.6 g, 26% yield) was 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) was added. The solution was stirred at r.t. for 48 h, then 3,4-dihydro-2H-pyran (1.6 mL) was 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 a membrane pump vacuum. The residue was purified by flash chromatography (silica, heptane/ethyl acetate gradient). 6-Bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (2.2 g, 38%) was obtained.

Workup

  1. temperaturecooled to r.t.
  2. extractionThe mixture was extracted twice with ethyl acetate
  3. washthe combined organic phases were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in a membrane pump vacuum

Sources & evidence

ORD record
ord-5cc275a5cf39434ab01b718e83630c4c
Source dataset
uspto-grants-2015_09
Patent number
US09133181B2

Reaction notes

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