Hydrochloric Acid → 4-(6-Chloro-pyrimidin-4-ylmethyl)-phenylamine

A 4 N solution of HCl in dioxane (11.7 mL, 46.9 mmol, 30 equiv) is added to a solution of [4-(6-chloro-pyrimidin-4-ylmethyl)-phenyl]-carbamic acid tert-butyl ester (Example 117) (0.50 g, 1.56 mmol) in CH2Cl2 (6.7 mL), under an argon atmosphere. The resulting white suspension is stirred at rt for 6.5 h. Additional 4 N HCl solution (1.1 mL, 4.6 mmol, 3.0 equiv) is added. The reaction mixture is allowed to stir for 0.5 h and concentrated in vacuo to afford 0.467 g of crude 4-(6-chloro-pyrimidin-4-ylmethyl)-phenylamine as a white solid. An 8 M solution of methylamine in EtOH (5.1 mL, 40.0 mmol, 30 equiv) Is added to a solution of crude 4-(6-chloro-pyrimidin-4-ylmethyl)phenylamine (0.300 g, 1.37 mmol) in EtOH (2.7 mL), under an argon atmosphere. The mixture Is heated to 50° C. (oil bath temperature) for 5 h, allowed to cool to rt and concentrated in vacuo. The residue is purified by silica gel (48 g) column chromatography (CH2Cl2/MeOH, 85/15) to afford the title compound as a light yellow oil: ES-MS: 215.0 [M+H]+; single peak at tR=3.03 min (System 2); Rf=0.49 (CH2Cl2/MeOH, 85/15).