Triphenylphosphine → Tert-butyl 4-{3-[(4-chloro-6-methoxyquinazolin-7-yl)oxy]propyl}piperazine-1-carboxylate

Participants

Reaction Steps

4-Chloro-7-hydroxy-6-methoxyquinazoline (1.7 g, 0.08 mmol), (prepared as described for the starting material in Example 4), tert-butyl 4-(3-hydroxypropyl)piperazine-1-carboxylate (2.17 g, 8.89 mmol), (prepared as described for the starting material in Example 15), and triphenylphosphine (2.97 g, 11.3 mmol) were added to dichloromethane (42.5 ml). Diisopropyl azodicarboxylate (1.91 ml, 9.70 mmol) was added and the reaction mixture stirred at ambient temperature for 1.5 hours and then concentrated under reduced pressure. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5 followed by 92/8) to give the product containing a single impurity. A second column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (96/4) gave tert-butyl 4-{3-[(4-chloro-6-methoxyquinazolin-7-yl)oxy]propyl}piperazine-1-carboxylate (3.0 g, 99%) as a white solid.

Provenance & Evidence