CONC(=O)c1ccccc1Nc1cc(Cl)ncc1Cl.Cc1cc(N)n(C(C)C)n1>C1COCCO1.CC(C)(C)[O-].CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.[Na+].[Pd]>CONC(=O)c1ccccc1Nc1cc(Nc2cc(C)nn2C(C)C)ncc1Cldioxane (4.3 mL) was added to 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (142 mg, 0.45 mmol), 1-isopropyl-3-methyl-1H-pyrazol-5-amine (127 mg, 0.91 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (52.6 mg, 0.09 mmol), BIS(DIBENZYLIDENEACETONE)PALLADIUM (39.2 mg, 0.07 mmol) and sodium 2-methylpropan-2-olate (65.6 mg, 0.68 mmol) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. Reaction mixture from EN04231/5 was combined and filtered through a PTFE cup to remove insoluble precipitate, washed filter with dioxane and combined filtrates were purified by ion exchange chromatography, using an 25g SCX-2 column. The desired product was eluted from the column using 7M NH3/MeOH and product fractions were evaporated to dryness to afford crude product (457 mg). The crude product was purified by flash silica (40g grace) chromatography, elution gradient 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (175 mg, 93 %) as a beige solid.
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