These common heterocyclic compound, 1192-21-8, name is 1-Methyl-1H-pyrazol-5-amine, its 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. Safety of 1-Methyl-1H-pyrazol-5-amine
3rd Generation BrettPhos precatalyst (22.95 mg, 0.03 mmol) was added to 2-(2-chloro-5- methylpyrimidin-4-yl)-7-((6-(difluoromethyl)pyridin-2-yl)methyl)-6,7- dihydroimidazo[l,2-a]pyrazin-8(5H)-one (Intermediate 51; 205 mg, 0.51 mmol), 1-methyl- lH-pyrazol-5-amine (123 mg, 1.27 mmol) and CS2CO3 (330 mg, 1.01 mmol) in 1,4- dioxane (8 mL) at 25°C under nitrogen and the resulting mixture was stirred at 100 °C for 8 hours. The solvent was then removed under reduced pressure. The crude product was purified by flash silica chromatography, elution gradient 0 to 6percent MeOH in DCM. Compound containing fractions were evaporated to dryness to afford a yellow residue. This residue was purified further by preparative HPLC (XSelect CSH Prep C18 OBD column, 5mu silica, 19 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.03percent NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 7-((6-(difluoromethyl)pyridin-2- yl)methyl)-2-(5-methyl-2-((l-methyl-lH-pyrazol-5-yl)amino)pyrimidin-4-yl)-6,7- dihydroimidazo[l,2-a]pyrazin-8(5H)-one (Example 15; 122 mg, 51.8percent) as a white solid. H NMR (400 MHz, DMSO, 20°C) delta 2.50 (3H, s), 3.70 (3H, s), 3.87 – 3.95 (2H, m), 4.42 – 4.50 (2H, m), 4.87 (2H, s), 6.30 (1H, d), 6.95 (1H, t), 7.33 (1H, d), 7.61 (2H, t), 7.94 (1H, s), 8.00 (1H, t), 8.32 (1H, s), 9.24 (1H, s). m/z (ES+), [M+H]+ = 466.
The synthetic route of 1-Methyl-1H-pyrazol-5-amine has been constantly updated, and we look forward to future research findings.
Reference:
Patent; ASTRAZENECA AB; WARD, Richard, Andrew; JONES, Clifford, David; SWALLOW, Steven; GRAHAM, Mark, Andrew; DOBSON, Andrew, Hornby; MCCABE, James, Francis; (223 pag.)WO2017/80979; (2017); A1;,
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