Benzyl 4-((5-chloro-2-pivalamidopyridin-4-ylamino)methyl)piperidine-1-carboxylate → 5-chloro-N4-(piperidin-4-ylmethyl)pyridine-2,4-diamine

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Reaction Steps

Benzyl 4-((5-chloro-2-pivalamidopyridin-4-ylamino)methyl)piperidine-1-carboxylate (0.52 g, 1.12 mmol) was refluxed in 6M HCl (20 mL) for 2 hr. The volatiles were removed in vacuo and the residue was dissolved in MeOH and adsorbed onto Isolute SCX-II acidic resin. The resin was washed with methanol, then 2M ammonia in methanol. The basic fractions were concentrated to give crude 5-chloro-N4-(piperidin-4-ylmethyl)pyridine-2,4-diamine (0.234 g, 96%). LCMS (4) Rt=0.51 min; m/z (ESI+) 241 (MH+). Di-tert-butyl dicarbonate (0.21 g, 1 eq.) in dichloromethane (1 mL) was added dropwise to 5-chloro-N4-(piperidin-4-ylmethyl)pyridine-2,4-diamine (0.228 g, 0.95 mmol) and triethylamine (0.40 ml, 3 eq.) in dichloromethane (6.5 mL). The solution was stirred at room temperature for 2 hr. Solvents were evaporated and the crude product was purified by preparative thin layer chromatography, eluting with 8% MeOH, 1% NH3, 91% dichloromethane, to give tert-butyl 4-((2-amino-5-chloropyridin-4-ylamino)methyl)piperidine-1-carboxylate (109 mg, 34%) as a white powder.

Provenance & Evidence