4-Pyridinemethanamine → 2-N-phenyl-4-N-(pyridin-4-ylmethyl)pyridine-2,4-diamine

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Pyridin-4-ylmethanamine (58.1 mg, 0.54 mmol), 4-chloro-N-phenylpyridin-2-amine (100 mg, 0.49 mmol) and sodium 2-methylpropan-2-olate (94 mg, 0.98 mmol) were suspended in DMA (2 mL) and sealed into a microwave tube. Nitrogen was bubbled through the reaction mixture for 5 minutes. (R)-(-)-1-[(S)-2-(DICYCLOHEXYLPHOSPHINO)FERROCENYL]ETHYLDI-T-BUTYLPHOSPHINE (32.5 mg, 0.06 mmol) and diacetoxypalladium (8.78 mg, 0.04 mmol) were added to the reaction mixture and nitrogen was bubbled through the reaction mixture for a further 5 minutes. The reaction was heated thermally to 100 °C for 30 mins under nitrogen and cooled to RT. The reaction mixture was neutralised with HCl and purified by ion exchange chromatography, using a 20 g SCX column. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM. Fractions containing product were evaporated to dryness to afford impure product. Impure product was purified by flash silica chromatography, elution gradient 3 to 8% MeOH in DCM. Fractions containing product were evaporated to dryness to afford impure product. Impure product was purified by preparative HPLC (Waters SunFire column, 5µ silica, 50 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness N2-phenyl-N4-(pyridin-4-ylmethyl)pyridine-2,4-diamine (31.2 mg, 23.11 %) as an off white solid.

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