CN(C)C1CCN(c2cccc(N)c2)C1.Cc1ccc(NC(=O)c2ccc3c(c2)OCCO3)cc1NC(=O)c1ccc(Cl)nc1>CC(C)(C)[O-].CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.Cc1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.[Na+].[Pd].[Pd]>Cc1ccc(NC(=O)c2ccc3c(c2)OCCO3)cc1NC(=O)c1ccc(Nc2cccc(N3CCC(N(C)C)C3)c2)nc1A mixture of 6-chloro-N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)nicotinamide (70 mg, 0.17 mmol),[Reactants],(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (5.73 mg, 9.91 µmol),TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (4.54 mg, 4.95 µmol),sodium 2-methylpropan-2-olate (23.81 mg, 0.25 mmol) in toluene (4 mL)/IPA (1.000 mL)was degassed with nitrogen and heated at reflux for 18 hours.The reaction mixture was filtered and filtered solid washed with ethyl acetate. The organic filtrate was washed with water (50ml), and organic layer dried over Na2SO4, filtered and evaporated.The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)-6-(3-(3-(dimethylamino)pyrrolidin-1-yl)phenylamino)nicotinamide (10.00 mg, 10.22 %) as a cream solid.
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