Method for preparing 5-chloro-N-({(5S)-2-oxo-3-[4-(5,6-dihydro-4H-[1,2,4]triazin-1-yl)phenyl]-1,3-oxazolidin-5-yl}methyl) derivative and intermediate used therein

摘要

Disclosed are: a method for preparing a 5-chloro-N-({(5S)-2-oxo-3-[4-(5,6-dihydro-4H-[1,2,4]triazin-1-yl)phenyl]-1,3-oxazolidin-5-yl}-methyl)thiophene-2-carboxamide derivative, which is a inhibitor of blood coagulation factor Xa, in a high purity and yield; and a novel intermedicate used therein.

主权项

1. A method for preparing an oxazolidinone derivative of formula (I) or a pharmaceutically acceptable salt thereof, comprising the steps of:
introducing an amino protecting group to a cyclic amidrazone of formula (V) to obtain a compound of formula (VI); reducing the nitro group of the compound of formula (VI) to obtain a compound of formula (VII); subjecting the compound of formula (VII) to a reaction with 5-chloro-N-(((S)-oxiran-2-yl)methyl)thiophene-2-carboxamide to obtain a compound of formula (VIII) having a chlorothiophene group; conducting a carbonylation reaction of the compound of formula (VIII) using a phosgene equivalent to obtain an oxazolidinone of formula (IX); and removing the amino protecting group from the amidrazone ring of the oxazolidinone of formula (IX), wherein, R′ is hydrogen, C1-C7 alkyl, C3-C7 cycloalkyl, or C4-C12 heteroaryl comprising 1 to 4 hetero atoms selected from the group consisting of oxygen, sulfur, and nitrogen; in which R′ may be optionally substituted with one or more substituents selected from the group consisting of C1-C7 alkyl, C1-C7 haloalkyl, C1-C7 alkoxy, and halogen; and PG is formyl, (C1-C7 alkyl)carbonyl, (C1-C7 haloalkyl)carbonyl, (C6-C12 aryl)carbonyl, (C1-C7 alkoxy)carbonyl, (C6-C12 aryl)(C1-C7 alkoxy)carbonyl, or trityl.