Sodium Carbonate → 1-Benzyl-4-(4-fluoro-2-methyl-phenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester

HRID 451215Notes

Reaction equation

HRID 451215 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7](Cl)=[C:8]2[CH:14]=[N:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:9]2=[N:10][CH:11]=1)=[O:5])[CH3:2].[F:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[C:26]([CH3:33])[CH:25]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.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>[CH2:1]([O:3][C:4]([C:6]1[C:7]([C:27]2[CH:28]=[CH:29][C:24]([F:23])=[CH:25][C:26]=2[CH3:33])=[C:8]2[CH:14]=[N:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:9]2=[N:10][CH:11]=1)=[O:5])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734665(4-Fluoro-2-methylphenyl)boronic acidHCID 21823886Ethyl 1-benzyl-4-chloro-1H-pyrazolo[3,4-B]pyridine-5-carboxylate

Product 1

HCID 674406501-Benzyl-4-(4-fluoro-2-methyl-phenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl esterYield 84.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
75 °C

Procedure

A solution of 1-benzyl-4-chloro-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester (4.56 g, 0.0144 mol) in toluene (80 mL) and EtOH (40 mL) was degassed 3 times before Pd(PPh3)4 (0.834 g, 0.722 mmol), 4-fluoro-2-methylphenylboronic acid (2.67 g, 0.0173 mol) and an aqueous solution of Na2CO3 (2N, 14.4 mL, 0.0288 mol) were added. The reaction mixture was stirred at 75° C. for 15 hours, cooled down to RT, filtered and the volatiles evaporated under vacuo. The residue was taken up in EtOAc and washed with aqueous NaOH (1N). The organic phase was dried over Na2SO4, concentrated under vacuo, before a purification on column chromatography (SiO2, EtOAc/Heptane, 1/4) yielded 4.74 g (84%) of the title compound as a colorless solid.

Workup

  1. temperaturecooled down to RT
  2. filtrationfiltered
  3. customthe volatiles evaporated under vacuo
  4. washwashed with aqueous NaOH (1N)
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated under vacuo, before a purification on column chromatography (SiO2, EtOAc/Heptane, 1/4)

Sources & evidence

ORD record
ord-a24695064c704485ba9a52fe18774334
Source dataset
uspto-grants-2013_07
Patent number
US08487102B2

Reaction notes

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