Water → 5-hydroxy-{6-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-pyridin-2-yl}-acetic acid methyl ester

HRID 886582Notes

Reaction equation

HRID 886582 reaction equation
[CH3:1][O:2][C:3](=[O:13])[CH:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8](Br)[N:7]=1)O.[CH3:14][O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22]1[C:30]2[C:25](=[N:26][CH:27]=[C:28](B3OC(C)(C)C(C)(C)O3)[CH:29]=2)[N:24]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])[N:23]=1.[OH2:48]>O1CCCC1.C(#N)C>[CH3:1][O:2][C:3](=[O:13])[CH2:4][C:6]1[CH:11]=[CH:10][C:9]([OH:48])=[C:8]([C:28]2[CH:29]=[C:30]3[C:22]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=4[O:15][CH3:14])=[N:23][N:24]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:45])([CH3:47])[CH3:46])[C:25]3=[N:26][CH:27]=2)[N:7]=1

Participants

5

Reactant 3

HCID 962WaterHCID 59825086Methyl 2-(6-bromopyridin-2-yl)-2-hydroxyacetateHCID 598360923-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxy-methyl)-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 692988445-hydroxy-{6-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-pyridin-2-yl}-acetic acid methyl esterYield 35%

Reagents, catalysts & solvents 1

HCID 22177404Acetonitrile tetrahydrofuranSolvent

Procedure

In a microwave vial (6-bromo-pyridin-2-yl)-hydroxy-acetic acid methyl ester (430.9 mg, 1.75 mmol), 3-(2-Methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (842.3 mg, 1.75 mmol) in tetrahydrofuran/acetonitrile/1 N aqueous sodium bicarbonate (20 ml) was degassed with nitrogen and 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichloromethane adduct (143.0 mg, 0.18 mmol) was added and the vial sealed. This reaction mixture was irradiated to 80° C. for 30 minutes in a microwave reactor. 100 ml water was added and this mixture was extracted with ethyl acetate (3×). The combined organic layers were dried over magnesium sulfate and purified by silica gel chromatography to yield 5-hydroxy-{6-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-pyridin-2-yl}-acetic acid methyl ester as a white solid (319 mg, 35% yield). MS: m/z 521.6 (M+H+).

Workup

  1. additionwas added
  2. customThis reaction mixture was irradiated to 80° C. for 30 minutes in a microwave reactor
  3. extractionthis mixture was extracted with ethyl acetate (3×)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-c4a348140080497f8944f4a6b575e2e5
Source dataset
uspto-grants-2012_08
Patent number
US08242280B2

Reaction notes

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