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.[Fe].[Na+].[O-]c1ccccc1.[Pd]>Cc1nn(C)cc1Nc1cc(Nc2cccc3c2C(=O)N(C)CC3)c(C#N)cn1
1,3-dimethyl-1H-pyrazol-4-amine (35.5 mg, 0.32 mmol), 6-chloro-4-(2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-ylamino)nicotinonitrile (50 mg, 0.16 mmol)sodium phenolate (18.56 mg, 0.16 mmol),(R)-(-)-1-[(S)-2-(DICYCLOHEXYLPHOSPHINO)FERROCENYL]ETHYLDI-T- BUTYLPHOSPHINE (8.74 mg, 0.02 mmol) and diacetoxypalladium (2.87 mg, 0.01 mmol) were suspended in DME (1 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. LCMS indicated 47% product, ~8% dimer, ~8% hydrolysed Starting material , Starting material 25% and an unknown 17% @ 2.66 and unknown 12% @ 0.77. Sample combined with en01521-027 and en01521-034, SCX'd and sent to purification group. 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 (34.0 mg, 54.9 %) as a brown solid.
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