US 12,570,660 B2 · Process for the preparation of a pyrimidino-diazepine derivative

Abstract

In one aspect, the invention relates to a process for preparing a compound of formula (XII), wherein PG is a protecting group, or a compound of formula (XI), comprising the steps of: (i) treating a compound of formula XIII, wherein PG is a protecting group, with N-methylpiperazine to form a compound of formula XII, wherein said compound of formula XII is in the form of a mixture of cis and trans isomers; (ii) combining the mixture formed in step (i) with an organic solvent and heating the solvent mixture so formed; (iii) isolating the trans-isomer of the compound of formula XII from the solvent mixture formed in step (ii); and (iv) optionally treating said trans-isomer of the compound of formula XII with an acid to form a compound of formula XI; and isolating said compound of formula XI. Further aspects of the invention relate to processes for preparing pyrimido-diazepinone derivatives using the above process and intermediates.

Claims20

Dependent claims

A process for preparing a compound of formula (XII), wherein PG is a protecting group selected from the group consisting of acetyl and tert-butoxycarbonyl (BOC), or a compound of formula (XI), comprising the steps of:

(i) treating a compound of formula XIII, wherein PG is a protecting group selected from the group consisting of acetyl and tert-butoxycarbonyl (BOC), with N-methylpiperazine to form a compound of formula XII, wherein said compound of formula XII is in the form of a mixture of cis and trans isomers;
(ii) combining the mixture formed in step (i) with an organic solvent and heating the solvent mixture so formed;
(iii) isolating the trans-isomer of the compound of formula XII from the solvent mixture formed in step (ii);
wherein step (iii) comprises cooling the mixture such that the trans-isomer of the compound of formula XII precipitates out of solution, filtering the precipitate so formed, and optionally washing and/or drying the precipitate;
and
(iv) optionally treating said trans-isomer of the compound of formula XII with an acid to form a compound of formula XI;
and isolating said compound of formula XI.

4 more elements

A process of preparing a compound of formula I, or a pharmaceutically acceptable salt thereof, which comprises the steps of:

(A) hydrogenating a compound of formula VIll in the presence of Raney nickel catalyst to form a compound of formula VII;
(B) contacting said compound of formula VII with cyclopentanone to form a compound of formula VI;
(C) contacting said compound of formula VI with a compound of formula IX to form a compound of formula V;
(D) treating said compound ot formula V with He powder in the presence of acetic acid to form a compound of formula IV;
(E) treating said compound of formula IV with Mel to form a compound of formula III;
(F) contacting said compound of formula III with a compound of formula X to form a compound of formula II;
(G) contacting said compound of formula II with a compound of formula XI to form a compound of formula I;
(H) isolating the compound of formula I;
and
(I) optionally converting said compound of formula I to a pharmaceutically acceptable salt form thereof.

7 more elements

Dependencies are inferred from the claim text.

Process for the preparation of a pyrimidino-diazepine derivative

Life of this patent

Process for the preparation of a pyrimidino-diazepine derivative

Life of this patent

Abstract

Claims20