4-Aminobenzonitrile → 4-(5-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile

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A mixture of 4-aminobenzonitrile (35 mg, 299 mmol), N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine (110 mg, 284 μmol), tris(dibenzylideneacetone)dipalladium(0) (10 mg, 11 μmol), and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (9 mg, 23 μmol) were suspended in THF (1 mL) and sealed. The mixture was sonicated until homogeneously mixed. Lithium bis(trimethylsilyl)amide (1.28 mL, 1280 mmol) was then added through a syringe, then mixed well with sonication. The reaction tube was heated via microwave to 120° C. for 15 min. The reaction mixture was cooled to room temperature, then partitioned between EtOAc (3×50 mL) and NaHCO3 (aq., sat). The organic layer was washed with brine, and extracted with HCl (aq., 1 N, 3×50 mL). The aqueous layers were combined and filtered through a layer of celite. The filter cake was rinsed with 1 N HCl. The filtrate was then cooled in ice and neutralized with NH4OH (aq., conc.) to pH 8, then extracted with EtOAc (4×50 mL). The organic layers were combined, washed with brine, dried over Na2SO4, and then concentrated to give a brown solid which was then triturated with MeOH to give a light brown solid upon filtration. The filter cake was air dried over the weekend to give 4-(5-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile. MS (ESI, pos. ion) m/z: 469.2

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