Method for producing 1,4-benzoxazine compound

摘要

The present invention provides an industrially advantageous method for producing a 1,4-benzoxazine compound useful as a medicine while avoiding safety and health risks. Specifically, the present invention provides a method for producing a 1,4-benzoxazine compound [A], which comprises the three steps in the following scheme, namely, a step of converting the amino group at 7-position in a compound [a] into a dimesylamino group, a step of coupling a compound [b] with a boronic acid compound, and a step of converting the 7-position in a compound [c] into a monomesylamino group.;;In the above scheme, Ms is a methanesulfonyl group, and each of R′ and R″ is a hydrogen atom etc.

主权项

1. A method for producing a compound of the following formula [c]:wherein Ms is a methanesulfonyl group,which comprises the following steps of:
(step a) reacting a compound of the following formula [a]:with methanesulfonyl halide in the presence of a base to produce a compound of the following formula [b]:wherein the symbol is the same as defined above,and
(step b) reacting said compound [b] with a boronic acid compound of the following formula [d]:wherein R and R′ are the same or different and each of them is a hydrogen atom or an alkyl group, or both of them combine together to form an alkylene group,or an equivalent thereof, in the presence of a copper catalyst, in the presence or absence of a base, and in the presence or absence of a ligand selected from the group consisting of a pyridine, an imidazole, 1,4-diazabicyclo[2.2.2]octane, pyrazine, and mixtures thereof.