Application of 1192-21-8, 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.
To a mixture of (i?)-2-(2-chloro-5-methylpyrimidin-4-yl)-7-(3,4-difluorobenzyl)-6- (methoxymethyl)-6,7-dihydroimidazo[l ,2-a]pyrazin-8(5H)-one (Intermediate 62; 104.7 g, 225.64 mmol), 1 -methyl- lH-pyrazol-5-amine (33.5 g, 338.47 mmol) in 2-methyl tetrahydrofuran (1200 mL) and CS2CO3 (147 g, 451.29 mmol) in water (120 mL) were added 2′-(dicyclohexylphosphanyl)-N,N-dimethyl-[l, -biphenyl]-2-amine (7.10 g, 18.05 mmol) and Pd2(dba)3 (8.27 g, 9.03 mmol) at 25 °C under nitrogen. The resulting mixture was degassed 3 times under nitrogen and then stirred at 70 °C for 24 hours. The reaction mixture was cooled to room temperature and the layers were separated. The organic layer was washed successively with water (500 mL), aqueous citric acid (IN, 600 mL) and water (200 mL). Silicycle (Si-SH, 150 g) was added to the organic layer at 40 °C and stirred for 20 hours. After filtration the filtrate was concentrated and the residue was purified by SFC chromatography using a Kromasil DIOL column, elution gradient 25percent EtOH/NH3 100/0.5 in C02, 140 bar. Pure fractions were evaporated to dryness to afford (i?)-7-(3,4- difluorobenzyl)-6-(methoxymethyl)-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 18; 72.6 g, 65percent) as a solid. NMR (500 MHz, DMSO) delta 2.51 (3H, s), 3.17 (3H, s), 3.30 (1H, dd), 3.39 (1H, dd), 3.69 (3H, s), 4.03 (1H, dtd), 4.38 (1H, d), 4.44 (1H, dd), 4.51 (1H, dd), 5.08 (1H, d), 6.30 (1H, d), 7.22 – 7.28 (1H, m), 7.33 (1H, d), 7.41 (1H, dt), 7.47 (1H, ddd), 7.93 (1H, s), 8.31 (1H, s), 9.21 (1H, s). m/z (ES+), [M+H]+ = 495
The synthetic route of 1192-21-8 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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