ETHYL 5-CHLORO-METHYL PYRAZOLE-4-CARBOXYLATE

To a solution of tBuONO (2.95 mL, 2.46 mmol) in acetonitrile(ACN) was added CuCl (1.76 g, 1.77 mmol), and then added 14 (2.5 g, 1.48 mmol) to the mixture in portions. The reaction was stirred at r.t. for 2 h, and then heated at 60°C for 1 h.After completion as TLC monitored, the reaction mixture was cooled to r.t. and diluted with 2 N aq. HCl, then extracted with DCM (3×). The combined phases were washed withbrine, dried over MgSO4, filtered, concentrated and purifiedby flash column chromatography to give 15 (2.08 g) in 75percentyield. 1H-NMR (300 MHz, CDCl3) δ: 7.90 (1H, s), 4.30 (2H, q, J=5.4 Hz), 3.86 (3H, s), 1.34 (3H, t, J=5.4 Hz).A solution of tert-butyl nitrite (2.95 ml, 2.46 mmol) in acetonitrile (50 ml) was added cuprous chloride (1.76 g 1.77 mmol) Ethyl 5-amino-1-methylpyrazole-4-carboxylate (2.5 g, 1.48 mmol) was added portionwise After stirring at room temperature for 1 hour, Then 65 ° C for 1 hour, The reaction is completed, until the reaction liquid cooled to room temperature, It was poured into 3N HC1, extracted with dichloromethane, and the organic layer was dried and evaporated to dryness. The product was purified by a rapid preparative column (2.08g) in a yield of 75percent.Step 1. REFERENCE [1328] to a solution of compound 282b (1.84 g, 9.76 mmol) was added NCS (2.61 g, 19.52 mmol) under N2 and the mixture was stirred at 160 C for 4h under N2. To the reaction mixture was added CCl4 (10 ml) and saturated aqueous NaHCO3 (10 ml) and the mixture was extracted with DCM (20 ml x 2), and then combined the organic layers and the organic phase was dried with over Na2SO4, filtered and the filtrate was concentrated in vacuum. The residue was purified by column chromatography (SiO2, petroleum ether/ethyl acetate = 5/1). Compound 282c (482 mg, yield: 22.14%) was obtained as a yellow solid. 1H NMR (400mhz, CDCl3) s 4.35 (q, j = 7.1 hz, 2h), 3.84 (s, 3h), 1.38 (t, j = 7.2 hz, 3h). MS (ESI) m/z (M+H)+222.9.[1327] to a solution of compound 282a (1.5 g, 9.73 mmol) was added NCS (2.6 g, 19.46 mmol) under N2. The mixture was stirred at 160 C for 3h. The reaction mixture was added CCl4 (10 ml) and saturated aqueous NaHCO3 (10 ml). The mixture was extracted with DCM (20 ml x 2), and then combined the organic layers and the organic phase was dried with over Na2SO4, filtered and the filtrate was concentrated in vacuum. Compound 282b (1.84 g, crude) was obtained as a brown oil, which was used for next step directly. MS (ESI) m/z (M+H)+188.9.

Molecular Weight:188.61
XLogP3:1.4
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:188.0352552
Monoisotopic Mass:188.0352552
Topological Polar Surface Area:44.1
Heavy Atom Count:12
Complexity:177
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes