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

To a stirred solution of 4, 6-dichloronicotinaldehyde (3 x 1.0 g, 1.0 eq) in DME (3 x 14 mL), hydrazine hydrate (3 x 1.14 g, 4.0 eq, 99percent) was added slowly in a vial. The vial was sealed and the contents heated at 75°C for 16 h. After TLC showed completion, the mixture was cooled to rt and diluted with water (3 x 10 mL) and EtOAc (3 x 10 mL). After combining all 3 mixtures, the layers were separated and the organic layer was washed with brine (20 mL), dried over anhydrous sodium sulphate, filtered and concentrated. The resulting crude was purified by flash chromatography (Combiflash® - Redisep, 12 g) using MeOH in DCM as eluent. The desired product was eluted at 1percent MeOH in DCM. The fractions with product were concentrated to obtain pure 6-chloro- lH-pyrazolo[4, 3-c]pyridine as yellow solid (1.4 g, 53.43percent, from 3 batches). 1H NMR (400 MHz, DMSO-dPart III-- Synthesis of 6-chloro-1H-pyrazolo[4, 3-c]pyridine [0232] 4, 6-Dichloropyridine-3-carbaldehyde (3.7 g, 32 mmol), hydrazine (3.5 mL, 1 10 mmol) and N, N-diisopropylethylamine (20 mL) were combined in DMA (100 mL) and stirred at 80 °C for four hours. Then, the solution was cooled to room temperature, diluted with EtOAc, and washed three times with water and then with brine. The organic solution was concentrated and the resulting mixture was precipitated from dichloromethane to give 6- chloro-lH-pyrazolo[4, 3-c]pyridine. Yield 2 g (41percent). LCMS (ESI): calc. CTo a reaction vessel containing a mixture of 4, 6-dichloronicotinaldehyde (300 g, 1.7 mol) in 1, 4- dioxane (1200 mL) was added hydrazine (50percent> in water)(360 mL, 3.6 mol). The reaction vessel was sealed and heated at 150 °C over 18 h. The mixture was cooled to room temperature, concentrated in vacuo, poured over water and filtered. The filter cake was washed with 20percent> EtOAc in hexanes and dried to afford 6-chloro-lH-pyrazolo[4, 3-c]pyridine (101.4 g, 38 percent>) as a light-yellow solid. LCMS (ESI) [M+H]

Molecular Weight:153.57
XLogP3:1.4
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