4,6-dichloro-3-Methyl-1H-pyrazolo[4,3-c]pyridine

Intermediate 4A mixture ofIntermediate 3 (3.55 g, 15.8 mmol) and 35percent aqueous hydrazine (35 ml) in ethanol (35 ml) was stirred at rt for 3.5 hours. The reaction mixture was added to ice and extracted with ethyl acetate. The organic phase was washed with brine, dried and concentrated. The residue was purified by flash column chromatography on silica gel eluting with 3:1 petrol- ethyl acetate to give an off-white coloured solid (1.71 g, 54percent). To a solution of 1-(2, 4, 6-trichloro-pyridin-3-yl)-ethanone (1, 75 gin ethanol, absolute (8, 75 mL) was added hydrazinehydrate (0, 76 mL). The reaction was stirred at room temperature over the weekend (40 h). The solvent was evaporated and water (10 mL) added. The aqueous phase was extracted with DCM (3 x 10 mL), the combined organic phases were dried (Na2504) and concentrated. The crude material was purified by Biotage Isolera FCC (5i02 50 g) eluting 10-30percent EtOAc in cyclohexane to give 0.74 g of product as an off white solid.Analysis: HPLC-MS: R1 = 1.15 mm (method P), M+H = 202/2041H NMR (DMSO, 500 MHz) 6 2.64 (3H, s), 7.64 (1 H, s)To a solution of 4, 6-dichloro-3-methyl-1 H-pyrazolo[4, 3-c]pyridine (550.00 mg) in dioxan (11.00 mL) under a nitrogen atmosphere was added trimethyloxonium tetrafluoroborate (563.70 mg). The reaction was stirred at room temperature for 1 h. NaHCO3 (10 mL) was added and the mixture extracted with DCM (3 x 10 mL). The combined organics were dried (Na2504), concentrated and the crude residue purified by Biotage Isolera FCC (5i02 10 g) 50 / 50 EtOAc / cyclohexane to give 380 mg of 6.2 (64.6%) as a white solid.Analysis: HPLC-MS: R1 = 1.16 mm (method P), M+H = 216/2181H NMR (CDCI3, 500 MHz) 62.84 (3H, s), 4.10 (3H, s), 7.39 (1H, s)

Molecular Weight:202.04
XLogP3:2.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:200.9860526
Monoisotopic Mass:200.9860526
Topological Polar Surface Area:41.6
Heavy Atom Count:12
Complexity:178
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes