1H-Pyrazolo[3,4-b]pyridine,3-methyl-(9CI)

White solid

Step 3: Step 3: 3-Methyl-lH-pyrazolo[3, 4b]pyridine. A solution of l-(2-chloropyridin-3-yl)ethanone (22 g, 0.1415 mol) and hydrazine hydrate 98percent (113 g, 2.21 mol) in ethanol (300 mL) was refluxed for 12 h. About 80percent of the ethanol was distilled off under reduced pressure using a rotary evaporator. The residue was allowed to come to room temperature. The precipitated solid was filtered and washed with water. The product was dried at 90 Step 3[00177] To a solution of l-(2-Chloropyridin-3-yl)ethanone (III) (0.311 g, 2 mmol) in n-butanol (10 mL) was added hydrazine hydrate (1.45 mL, 30 mmol). The reaction was refluxed overnight. The solution was cooled and the solvent was evaporated under vacuum. The residue was dissolved in DCM and washed successively by water and brine. The organic layers were dried over MgS0To a solution of 1-(2-Chloropyridin-3-yl)ethanone (XIII) (0.311 g, 2 mmol) in n-butanol (10 mL) was added hydrazine hydrate (1.45 mL, 30 mmol). The reaction was refluxed overnight. The solution was cooled and the solvent was evaporated under vacuum. The residue was dissolved in DCM and washed successively by water and brine. The organic layers were dried over MgSOStep 3 To a solution of 1-(2-chloropyridin-3-yl)ethanone (XI) (0.31 1 g, 2 mmol) in n-butanol (10 mL) was added hydrazine hydrate (1.45 mL, 30 mmol). The reaction was refluxed overnight. The solution was cooled and the solvent was evaporated under vacuum. The residue was dissolved in DCM and washed successively by water and brine. The organic layers were dried over MgSO4, filtered and concentrated under reduced pressure to give 3-methyl-1H-pyrazolo [3, 4-b]pyridine (XII) as a white solid (192 mg, 1.44 mmol, 72percent yield). 1H NMR (CDCl3) δ ppm 2.64 (s, 3 H), 7.14 (dd, J=8.01Hz, J=4.62Hz, 1H), 8.14 (dd, J=7.54Hz, J=1.88Hz, 1H), 8.59 (dd, J=4.52Hz, J=1.32Hz, 1H), 1 1.68 (brs, 1H).Example 2(1)3-Methyl-1H-pyrazolo[3, 4-b]pyridine (2a)Normal-butyllithium (a 2.6 M solution in hexane, 87.0 mL) was dropwise added to a solution of N, N-diisopropylamine (11.2 mL) in THF (100 mL) at -78° C. under a nitrogen atmosphere, followed by increasing the temperature to 0° C. Then, the solution was cooled to -78° C., and a solution of 2-fluoropyridine (6.2 g) in THF (100 mL) was dropwise added thereto at -78° C., followed by stirring for 1 hr. Subsequently, a solution of N-methoxy-N-methylacetamide (8.46 mL) in THF (50 mL) was dropwise added to the reaction solution at -78° C., and then hydrazine monohydrate (31.9 mL) was added thereto, followed by stirring at 60° C. for 1 hr. After distillation of the solvent, water was added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with saturated saline. The organic layer after the washing was dried over anhydrous sodium sulfate, and then the solvent was distilled away to obtain compound (2a) (5.90 g, 69percent) as a white solid.General procedure: To a solution of the appropriate NH-aromatic heterocycle (1.0 mmol) in anhydrous N, N-dimethylformamide (3 mL) at 0 C was added sodium hydride (60% dispersion in mineral oil, 60 mg, 1.5 eq., 1.5 mmol) and the mixture stirred for 5 min before the appropriate alkyl halide (1.2 eq.) in N, N-dimethylformamide (1-3 mL) was added dropwise. The mixture was stirred until the starting material was consumed, as determined by thin-layer chromatography. The reaction mixture was quenched with saturated aqueous ammonium chloride (20 mL) and extracted with ethyl acetate (3 × 20 mL). The combined organic extracts were washed with water (3 × 20 mL) and aqueous lithium chloride (1 M, 20 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure.

Molecular Weight:133.15
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:133.063997236
Monoisotopic Mass:133.063997236
Topological Polar Surface Area:41.6
Heavy Atom Count:10
Complexity:126
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes