1,2-Dimethoxyethane → HCID 57969703, compound

HRID 384056Notes

Reaction equation

HRID 384056 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:17]([CH3:21])([CH3:20])[C:18]#[N:19])[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][N:15]=[CH:16][C:9]=23)[CH:7]=1.[C:22]1(B(O)O)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:14]1[C:10]2=[N:11][CH:12]=[CH:13][C:8]([C:6]3[CH:5]=[C:4]([C:17]([CH3:21])([CH3:20])[C:18]#[N:19])[CH:3]=[C:2]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:7]=3)=[C:9]2[CH:16]=[N:15]1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 42635199HCID 42635199, compound

Product 1

HCID 57969703HCID 57969703, compoundYield 34.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 2-(3-bromo-5-(1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl)-2-methylpropanenitrile (50 mg, 0.147 mmol) and phenyl boronic acid (26.76 mg, 0.220 mmol) were placed in a microwave vial. Ethylene glycol dimethyl ether (1.5 ml) was then added followed by sodium carbonate (269.0 mg, 243.9 μL of 2 M, 0.488 mmol) and tetrakis(triphenylphosphine)palladium(0) (14.2 mg, 0.012 mmol). The reaction mixture was heated under microwave irradiation at 150° C. for 60 minutes. The reaction mixture was allowed to cool down to room temperature and was diluted with ethyl acetate and water. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a white solid (17 mg, 34% yield).

Workup

  1. temperatureto cool down to room temperature
  2. dry with materialThe organic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  6. customThe fractions were collected
  7. customfreeze-dried

Sources & evidence

ORD record
ord-f81e8c04ab0943769c0c9b77fc548b32
Source dataset
uspto-grants-2013_02
Patent number
US08367697B2

Reaction notes

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