6-chloro-1H-pyrazolo[3,4-b]pyridine

To the solution of 6-chloro-2-fluoropyridine-3-carboxaldehyde (4gm, 25.lmmol) in THF (30mL), was added hydrazine hydrate (2.5 15gm, 56.3mmol) and the reaction mixture was heated60°C for 5h. The reaction mixture was concentrated and quenched with ice water. The solid was filtered and dried under vacuum to obtain the title compound (3.5gm, 92percent).‘HNMR (DMSO-d6, 300MHz): ö 13.8 (s, 1H), 8.32-8.29 (d, 1H), 8.20 (s, 1H), 7.27-7.24 (d, 1H). LCMS: 89.96percent, mlz = 153.9 (M+1).In n-butanol (6 L), 2, 6-dichloro-3-pyridinecarboxaldehyde (1056 g, 6.0 mol, 1 eq.) was added and hydrazine hydrate (1060g, 18.0mol, 3eq., 85percent), stirred at room temperature for 0.5h. The mixture was warmed to reflux overnight (16 h), filtered and evaporated. The crude product is then beaten with water/isopropyl alcohol (ν/ν = 7:1), filtered and dried. The product 6-chloro-1 hydrogen-pyrazolo[3, 4-B]pyridine (774 g, 5.0 mol) was obtained as a yellow powdery solid. The yield was 84percent and the purity was 98percent.6-Chloro-l//-pyrazolo[4, 3-b]pyridine (CAS: 63725-51-9; 0.35 g, 2.25 mmol) was added to a stirred solution of trimethyloxoniumtetrafluoroborate (CAS: 420-37-1; 1.35 g, 9.13 mmol)and DIPEA (1.93 mL, 11.23 mmol) in DCM (13.8 mL). The mixture was stirred at rt for 72 h and quenched with a saturated solution of NaHC03 and extracted with DCM. The organic layer was separated, dried (Na2S04), filtered and the solvent was evaporated in vacuo. The residue was purified by flash column chromatography (Si02; EtOAc in heptane, gradient from 20/80 to 100/0). The desired fractions were collected and concentrated in vacuo to yield intermediate 15a as a white solid (0.27 g, 65%).

Molecular Weight:153.57
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:153.0093748
Monoisotopic Mass:153.0093748
Topological Polar Surface Area:41.6
Heavy Atom Count:10
Complexity:130
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes