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US 11,111,236 B2Granted
Method for preparing oxaspirocycle derivative, and intermediate thereof
AssigneeJiangsu Hengrui Medicine Co., Ltd.
InventorsWenhai Li, Weixing Qi, Zhenjun Qiu
Life of this patent
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Abstract
A method for preparing an oxaspirocycle derivative and an intermediate thereof are described. The method reduces reaction steps, improves reaction yield, is simple and easy to operate, and is favorable for industrial large-scale production.
Claims15
A method for preparing a compound represented by formula D1 or a salt thereof,
- comprising separating optical isomers of a compound represented by formula D or a salt thereof, by a chemical resolution method:
- wherein,
- R is aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, halogen, amino, nitro, cyano, oxo, alkenyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, OR3, C(O)R3, C(O)OR3, S(O)mR3 and NR4R5;
- R3 is selected from the group consisting of hydrogen, alkyl, deuterated alkyl, amino, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from the group consisting of alkyl, halogen, hydroxyl, amino, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- each of R4 and R5 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, hydroxyalkyl, hydroxyl, amino, carboxylic ester group, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from the group consisting of alkyl, halogen, hydroxyl, amino, carboxylic ester group, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- and
- m is 0, 1 or 2;
- wherein a resolving agent is used in the chemical resolution method, and the resolving agent is a basic chiral resolving agent selected from the group consisting of S-phenylethylamine, quinidine, cinchonidine and arginine.
5 more elements
A compound represented by formula D1 or a salt thereof,
- wherein,
- R is aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted by one or more substituents selected front the group consisting of alkyl, haloalkyl, halogen, amino, nitro, cyano, oxo, alkenyl, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, OR3, C(O)R3, C(O)OR3, S(O)mR3 and NR4R5;
- R3 is selected from the group consisting of hydrogen, alkyl, deuterated alkyl, amino, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from the group consisting of alkyl, halogen, hydroxyl, amino, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- each of R4 and R5 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, hydroxyalkyl, hydroxyl, amino, carboxylic ester group, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from the group consisting of alkyl, halogen, hydroxyl, amino, carboxylic ester group, nitro, cyano, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- and
- m is 0, 1 or 2;
- and wherein the compound has an enantiomeric excess (ee) value of more than 99%.
4 more elements
Dependencies are inferred from the claim text.