反应 #131

ord-2e4132c3c32149d3a68cd64301eacce5

反应方程式

CN1CCc2cccc(Nc3cc(Cl)ncc3C#N)c2C1=O
CN1CCc2cccc(Nc3cc(Cl
Cc1nn(C)cc1N
Cc1nn(C)cc1N
Cc1nn(C)cc1Nc1cc(Nc2cccc3c2C(=O)N(C)CC3)c(C#N)cn1
Cc1nn(C)cc1Nc1cc(Nc2
收率 7.3%

溶剂

反应条件

温度
90°CELSIUS

实验过程

6-chloro-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (595 mg, 1.90 mmol), Palladium(II) acetate (34.2 mg, 0.15 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (132 mg, 0.23 mmol), 1,3-dimethyl-1H-pyrazol-4-amine (423 mg, 3.80 mmol) and Cesium carbonate (744 mg, 2.28 mmol) were suspended in dioxane (40 mL). The reaction was purged for 5 mins with nitrogen and then heated to 90 °C for 2 hour with stirring. The reaction was cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired crude product was eluted from the column using 7M NH3/MeOH and fractions were evaporated to dryness to afford crude product .The crude product was purified by preparative basic HPLC. Fractions containing the desired compound were evaporated to dryness to afford 6-(1,3-dimethyl-1H-pyrazol-4-ylamino)-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (54.0 mg, 7.33 %) as a beige solid.

来源

750 AstraZeneca ELN dataset