Method for preparing pyrroloaminopyridazinone compound and intermediates thereof
AssigneesJiangsu Hengrui Medicine Co., Ltd., Shanghai Shengdi Pharmaceutical Co., Ltd.
InventorsLingjian ZHU, Zhongjun GUAN, Wei JIANG, Jian HUANG
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Abstract
The present invention relates to a method for preparing a pyrroloaminopyridazinone compound and intermediates thereof. Specifically relating to a method for preparing the compound of formula (I), the target product being prepared by means of changing the starting materials and intermediates; the present method has the advantages of reactants such as the starting materials being easy to purchase, the reaction conditions being simple and controllable, the post-reaction treatment method being simple, the yield being high, and being beneficial for industrial production.
Claims21
1-35. (canceled)
A compound of formula (E), a salt thereof, or a stereoisomer thereof,
- wherein,
- Ra is selected from the group consisting of hydrogen, halogen, hydroxy, nitro, cyano, carboxy, amino, alkyl, haloalkyl, haloalkoxy and alkoxy;
- R3 is selected from the group consisting of hydrogen, halogen, alkyl, —OR1, —NHR2, —NR2R2 and alkylsulfonamido;
- R1 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, cycloalkyl, cycloalkylcarbonyl, heterocyclyl, heterocyclylcarbonyl, aryl, arylcarbonyl, heteroaryl and heteroarylcarbonyl;
- R2 is selected from the group consisting of hydrogen, alkyl, alkylamino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, cycloalkyl, cycloalkylcarbonyl, heterocyclyl, heterocyclylcarbonyl, aryl, arylcarbonyl, heteroaryl and heteroarylcarbonyl;
- G is selected from the group consisting of aryl, heteroaryl, cycloalkyl and heterocyclyl;
- G1 is selected from the group consisting of hydrogen and a hydroxy protecting group;
- L is an alkylene or absent;
- Y is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl;
- and
- m is 0, 1, 2 or 3.
A method for preparing the compound of formula (E1) or a stereoisomer thereof, wherein the method comprises a step of:
A compound of formula (B), a salt thereof, or a stereoisomer thereof,
- wherein,
- Ra is selected from the group consisting of hydrogen, halogen, hydroxy, nitro, cyano, carboxy, amino, alkyl, haloalkyl, haloalkoxy and alkoxy;
- R2 is selected from the group consisting of hydrogen, alkyl, alkylamino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, cycloalkyl, cycloalkylcarbonyl, heterocyclyl, heterocyclylcarbonyl, aryl, arylcarbonyl, heteroaryl and heteroarylcarbonyl;
- G is selected from the group consisting of aryl, heteroaryl, cycloalkyl and heterocyclyl;
- L is an alkylene or absent;
- Y is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl;
- m is 0, 1, 2 or 3;
- and
- R4 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, alkylsulfonyl, cycloalkyl, heterocyclyl, aryl and heteroaryl.
A method for preparing the compound of formula (B) or a stereoisomer thereof, wherein the method comprises a step of:
- wherein, Ra is selected from the group consisting of hydrogen, halogen, hydroxy, nitro, cyano, carboxy, amino, alkyl, haloalkyl, haloalkoxy and alkoxy;
- R2 is selected from the group consisting of hydrogen, alkyl, alkylamino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, cycloalkyl, cycloalkylcarbonyl, heterocyclyl, heterocyclylcarbonyl, aryl, arylcarbonyl, heteroaryl and heteroarylcarbonyl;
- G is selected from the group consisting of aryl, heteroaryl, cycloalkyl and heterocyclyl;
- L is an alkylene or absent;
- Y is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl;
- and
- m is 0, 1, 2 or 3;
- and
- R4 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, alkylsulfonyl, cycloalkyl, heterocyclyl, aryl and heteroaryl.
A method for preparing the compound of formula (A) or a stereoisomer thereof, wherein the method comprises a step of:
- wherein,
- Ra is selected from the group consisting of hydrogen, halogen, hydroxy, nitro, cyano, carboxy, amino, alkyl, haloalkyl, haloalkoxy and alkoxy;
- R2 is selected from the group consisting of hydrogen, alkyl, alkylamino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, cycloalkyl, cycloalkylcarbonyl, heterocyclyl, heterocyclylcarbonyl, aryl, arylcarbonyl, heteroaryl and heteroarylcarbonyl;
- G is selected from the group consisting of aryl, heteroaryl, cycloalkyl and heterocyclyl;
- L is an alkylene or absent;
- Y is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl;
- and
- m is 0, 1, 2 or 3;
- and
- R4 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, alkylsulfonyl, cycloalkyl, heterocyclyl, aryl and heteroaryl.
A compound of formula (C), a salt thereof, or a stereoisomer thereof,
- wherein,
- Ra is selected from the group consisting of hydrogen, halogen, hydroxy, nitro, cyano, carboxy, amino, alkyl, haloalkyl, haloalkoxy and alkoxy;
- R2 is selected from the group consisting of hydrogen, alkyl, alkylamino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, cycloalkyl, cycloalkylcarbonyl, heterocyclyl, heterocyclylcarbonyl, aryl, arylcarbonyl, heteroaryl and heteroarylcarbonyl;
- G is selected from the group consisting of aryl, heteroaryl, cycloalkyl and heterocyclyl;
- L is an alkylene or absent;
- Y is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl;
- and
- m is 0, 1, 2 or 3.
Dependencies are inferred from the claim text.