CN1CCc2cccc(Nc3cc(Cl)ncc3C#N)c2C1=O.Cc1nn(C)cc1N>C1CCCC1.CC(=O)O.CC(=O)O.CC(C1CCCC1P(C1CCCCC1)C1CCCCC1)P(C(C)(C)C)C(C)(C)C.COCCOC.O=C([O-])[O-].[Cs+].[Cs+].[Fe].[Pd]>Cc1nn(C)cc1Nc1cc(Nc2cccc3c2C(=O)N(C)CC3)c(C#N)cn1
1,3-dimethyl-1H-pyrazol-4-amine (355 mg, 3.19 mmol), 6-chloro-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (500 mg, 1.60 mmol), Cesium carbonate (625 mg, 1.92 mmol), Palladium(II) acetate (28.7 mg, 0.13 mmol)and (R)-(-)-1-[(S)-2-(DICYCLOHEXYLPHOSPHINO)FERROCENYL]ETHYLDI-T-BUTYLPHOSPHINE (87 mg, 0.16 mmol) were suspended in DME (10 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness. The crude product was handed to the purification group and purified by basic preparative 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 (271 mg, 43.8 %) as a brown solid.
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