Application of 34334-96-8,Some common heterocyclic compound, 34334-96-8, name is 3-Methyl-5-nitro-1H-pyrazole, molecular formula is C4H5N3O2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
General procedure: Mcthancsulfonyl chloride (6.683 mL, 1.48 g/mL, 86.338 mmol) was added to a solution of 3-methoxy-3-methylbutanol (5 g, 42.31 mmol ) and Et-,N (17.661 mL, 0.728 g/mL, 127.059 mmol ) in DCM (477.33 mL, 1 .326 g/mL, 7452.28 mmol) at rt and the reaction mixture was stirred for 18h. Water was added. The organic layer was separated, washed with I N HCI(aq) then with brine before drying over MgSC>4. The organic layer was filtered and evaporated to afford a mixture on intermediate 778 and 778′ (10.3 g, quantitative yield ) that was used directly in the next step. Bromo-3-methoxypropane (1.20 mL, 10.51 mmol) was added at rt to a mixture of 5-nitro-lH-pyrazole (1.00 g, 8.84 mmol), 2 (2.35 g, 17.00 mmol) in DMF (10 mL).This reaction was stirred in a sealed tube at 120 C using one single mode microwave(Biotage Initiator EXP 60) with a power output ranging from 0 to 400 W for 30 min.Then, water was added and this mixture was extracted twice with EtOAc. The organic10 layers were mixed, dried over MgS04, filtered and the solvent was evaporated untildryness. The residue was purified by column chromatography on silica gel (IrregularSiOH, 40 |im, 80 g, mobile phase: gradient from 70% heptane, 29% EtOAc, 1% MeOH(+10% NH4OH) to 40% heptane, 52% EtOAc, 8% MeOH (+10% NH4OH)). The purefractions were collected and the solvent was evaporated until dryness to give 1.39 g of15 intermediate 56 (85% yield) and 267 mg of intermediate 56? (16% yield). Theseintermediates were used as it in the next step.
The synthetic route of 34334-96-8 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; JANSSEN PHARMACEUTICA NV; STANSFIELD, Ian; QUEROLLE, Olivier, Alexis, Georges; LIGNY, Yannick, Aime, Eddy; GROSS, Gerhard, Max; JACOBY, Edgar; MEERPOEL, Lieven; GREEN, Simon, Richard; HYND, George; KULAGOWSKI, Janusz, Jozef; MACLEOD, Calum; MANN, Samuel, Edward; (472 pag.)WO2018/2217; (2018); A1;,
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