Research on new synthetic routes about 1-Methyl-1H-pyrazole-3-carboxylic acid

The synthetic route of 25016-20-0 has been constantly updated, and we look forward to future research findings.

25016-20-0, name is 1-Methyl-1H-pyrazole-3-carboxylic acid, belongs to pyrazoles-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Safety of 1-Methyl-1H-pyrazole-3-carboxylic acid

Examples 213 to 239 General ProcedureThe carboxylic acid R’COOH (0.12 mmol) is treated with a solution of HATU (0.12 mmol) in DMF (0.25 ml) and DIPEA (0.052 ml, ca. 0.3 mmol) is added. The solution is shaken for 10 mins, and is treated with a solution of Intermediate 15 or 16 (0.1 mmol) in DMF (0.2 ml). The resulting solution is shaken for 10 mins and left to stand for 18 h (e.g. at room temperature), and then the DMF is removed in a Genevac vacuum centrifuge. The residue is dissolved in chloroform (0.3 ml), is applied to an SPE cartridge (1 g, aminopropyl) which has been pre-washed with chloroform (6 ml), and is eluted sequentially with chloroform (3 ml) and 10% methanol in ethyl acetate (3 ml). Fractions containing the desired product are concentrated in vacuo in a Genevac vacuum centrifuge, and where necessary the residue is purified by mass directed autoprep HPLC (e.g. acetonitrile/water). Where necessary, the compound(s) is/are dissolved in chloroform, and is/are further purified by loading onto a SPE cartridge (0.5 g, aminopropyl) which has been prewashed with chloroform, eluting with 10% methanol in ethyl acetate.; Example 238 (Synthesis B) N-{[(1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1-methyl-1H-pyrazole-3-carboxamide An example of a specific synthesis (Synthesis B) of Example 238 is as follows:HATU (1.095 g) was dissolved in DMF (6 ml) and an aliquot (0.25 ml) of this solution added to 1-methyl-1H-pyrazole-3-carboxylic acid (0.12 mmol). DIPEA (0.052 ml) was added and the solution shaken for 10 mins. Meanwhile Intermediate 16 (364 mg) was dissolved in DMF (2.4 ml) and an aliquot (0.2 ml) of this solution added. The solution was shaken for 10 min and left to stand for 18 h. DMF was removed in a Genevac vacuum centrifuge and the residue dissolved in chloroform (0.3 ml) and applied to an SPE cartridge (1 g, aminopropyl) pre-washed with chloroform (6 ml). The cartridge was eluted with chloroform (3 ml) and the solvent removed in a Genevac. The residue was dissolved in 50% DMSO in methanol (0.5 ml) and purified by mass directed autoprep HPLC followed by SPE cartridge (0.5 g, Flash NH2) eluting with 10% methanol in ethyl acetate to give Example 238 (20.7 mg). LCMS showed MH+=462; TRET=1.87 min.

The synthetic route of 25016-20-0 has been constantly updated, and we look forward to future research findings.