Water → 5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-2-(2-oxo-oxazolidin-3-yl)-benzamide

HRID 1865657Notes

Reaction equation

HRID 1865657 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N:13]2[CH2:17][CH2:16][O:15][C:14]2=[O:18])=[C:6]([CH:12]=1)[C:7]([N:9]([CH3:11])[CH3:10])=[O:8].[CH3:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]1[C:35]2[C:30](=[N:31][CH:32]=[C:33](B3OC(C)(C)C(C)(C)O3)[CH:34]=2)[N:29]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[N:28]=1.O>O1CCCC1.C(#N)C>[CH3:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]1[C:35]2[C:30](=[N:31][CH:32]=[C:33]([C:2]3[CH:3]=[CH:4][C:5]([N:13]4[CH2:17][CH2:16][O:15][C:14]4=[O:18])=[C:6]([CH:12]=3)[C:7]([N:9]([CH3:11])[CH3:10])=[O:8])[CH:34]=2)[N:29]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:50])([CH3:52])[CH3:51])[N:28]=1

Participants

5

Reactant 3

HCID 962WaterHCID 579757195-bromo-N,N-dimethyl-2-(2-oxo-oxazolidin-3-yl)-benzamideHCID 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 686629715-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-2-(2-oxo-oxazolidin-3-yl)-benzamide

Reagents, catalysts & solvents 1

HCID 22177404Acetonitrile tetrahydrofuranSolvent

Procedure

In a microwave vial 5-bromo-N,N-dimethyl-2-(2-oxo-oxazolidin-3-yl)-benzamide (150 mg, 0.45 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 (2.169 g, 0.45 mmol) in tetrahydrofuran/acetonitrile/1 N aqueous sodium bicarbonate (4 ml) was degassed with nitrogen and 1,1′-bis(diphenylphosphino) ferrocenepalladium(II)-dichloride dichloromethane adduct (36.8 mg, 0.05 mmol) was added and the vial sealed. This reaction mixture was irradiated to 100° 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 crude 5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-2-(2-oxo-oxazolidin-3-yl)-benzamide which was dissolved in 2 ml trifluoroacetic acid and stirred for 16 hours. The volatiles were removed and the residue purified by preparative mass-triggered reverse-phase HPLC to give 5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-2-(2-oxo-oxazolidin-3-yl)-benzamide as a white solid (62 mg, 49% yield). 1H NMR (500 MHz, DMSO-d6) δ 2.92 (s, 3H); 2.97 (s, 3H); 3.57 (s, 3H); 3.99 (m, 2H); 7.10 (t, J=8 Hz 1H) 7.23 (d, J=8 Hz 1H); 7.47 (t, J=8 Hz, 1H); 7.58 (d, J=8 Hz 1H); 7.66 (d, J=8 Hz 1H); 7.74 (s, 1H); 7.89 (d, J=8 Hz 1H); 8.39 (s, 1H); 8.89 (s, 1H); 13.83 (s, br, 1H) MS: m/z 458.5 (M+H+).

Workup

  1. additionwas added
  2. customThis reaction mixture was irradiated to 100° 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-a283acfb6c0248f2b5aa41e5f30ff4f8
Source dataset
uspto-grants-2009_12
Patent number
US07626021B2

Reaction notes

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