Potassium Carbonate → 1h-Pyrazolo[3,4-c]pyridine-5-carboxylic acid,1-[(4-fluorophenyl)methyl]-,methyl ester

HRID 2377070Notes

Reaction equation

HRID 2377070 reaction equation
[NH:1]1[C:5]2=[CH:6][N:7]=[C:8]([C:10]([O:12][CH3:13])=[O:11])[CH:9]=[C:4]2[CH:3]=[N:2]1.[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Br)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+].C(=O)(O)[O-].[Na+]>CN(C=O)C.C(Cl)(Cl)Cl>[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][N:1]2[C:5]3=[CH:6][N:7]=[C:8]([C:10]([O:12][CH3:13])=[O:11])[CH:9]=[C:4]3[CH:3]=[N:2]2)=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 680214-Fluorobenzyl bromideHCID 516892Sodium BicarbonateHCID 59855813Methyl 1H-pyrazolo[3,4-C]pyridine-5-carboxylate

Product 1

HCID 691988241h-Pyrazolo[3,4-c]pyridine-5-carboxylic acid,1-[(4-fluorophenyl)methyl]-,methyl esterYield 65.3%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of methyl 1H-pyrazolo[3,4-c]pyridine-5-carboxylate (0.628 g, 3.545 mmol) in DMF (15 mL) was added 4-fluorobenzyl bromide (0.442 mL, 3.545 mmol) followed by potassium carbonate (0.490 g, 3.545 mmol), and the mixture was stirred overnight at room temperature. Saturated sodium bicarbonate was added and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The crude solid was purified by flash column chromatography (silica gel, 0-20% acetonitrile:chloroform v/v) to provide pure desired methyl 1-(4-fluorobenzyl)-1H-pyrazolo[3,4-c]pyridine-5-carboxylate (0.66 g, 30% yield over three steps) and the undesired methyl 2-(4-fluoro-benzyl)-2H-pyrazolo[3,4-c]pyridine-5-carboxylate (0.73 g, 33% yield) as white solids. Methyl 1-(4-fluorobenzyl)-1H-pyrazolo[3,4-c]pyridine-5-carboxylate: 1HNMR (CDCl3, 300 MHz) δ ppm 8.91 (s, 1H), 8.59 (s, 1H), 8.22 (s, 1H), 7.26 (m, 2H), 7.02 (m, 2H), 5.69 (s, 2H), 4.03 (s, 3H). LCMS (API-ES M+H+) 286. Methyl 2-(4-fluoro-benzyl)-2H-pyrazolo[3,4-c]pyridine-5-carboxylate: 1HNMR (CDCl3, 300 MHz): 6 ppm 9.32 (s, 1H), 8.51 (s, 1H), 8.10 (s, 1H), 7.36 (m, 2H), 7.09 (m, 2H), 5.65 (2H, s), 4.02 (s, 3H). LCMS (API-ES M+H+) 286.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
  2. dry with materialThe combined organic extracts were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude solid was purified by flash column chromatography (silica gel, 0-20% acetonitrile

Sources & evidence

ORD record
ord-171839e3900d44b894e6ebdb32c2e11e
Source dataset
uspto-grants-2008_12
Patent number
US07468375B2

Reaction notes

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