POCl3 chlorination of 4-quinazolones.

The reaction of quinazolones with POCl(3) to form the corresponding chloroquinazolines occurs in two distinct stages, which can be separated through appropriate temperature control. An initial phosphorylation reaction occurs readily under basic conditions (R(3)N, aq pK(a) > 9) at t < 25 °C to give a variety of phosphorylated intermediates. Pseudodimer formation, arising from reaction between phosphorylated intermediates and unreacted quinazolone, is completely suppressed at these temperatures, provided the system remains basic throughout the POCl(3)addition.

Kinetics and mechanism of N-Boc cleavage: evidence of a second-order dependence upon acid concentration.

The kinetics of the HCl-catalyzed deprotection of the Boc-protected amine, thioester 2 to liberate AZD3409 1 have been studied in a mixture of toluene and propan-2-ol. The reaction rate was found to exhibit a second-order dependence upon the HCl concentration. This behavior was found to have a degree of generality as the deprotection of a second Boc-protected amine, tosylate 3 to yield amine 4 using HCl, sulfuric acid, and methane sulfonic acid showed the same kinetic dependence.