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US 10,501,468 B2Granted
Method for preparing intermediate of 6-arylaminopyridonecarboxamide compound as MEK inhibitor
AssigneesChia Tai Tianqing Pharmaceutical Group Co., Ltd., Centaurus Biopharma Co., Ltd.
InventorsLulu Wang, Fei Liu, Yizhong Zhu, Hongying Zhang
Life of this patent
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Abstract
Provided is a method for preparing an intermediate of 6-arylaminopyridonecarboxamide compound as an MEK inhibitor, comprising preparing a compound of formula (III) as an intermediate of 6-arylaminopyridonecarboxamide compound using a compound of formula V as a raw material.
Claims18
A method for preparing a compound of formula III, comprising reacting a compound of formula IV with a compound of formula V,
- wherein Ra and Rb are each independently selected from the group consisting of hydrogen and C1-C6 alkyl;
- represents X—Y═W or X═Y—W;
- X and W are independently selected from the group consisting of N, O, S, and CR2;
- Y is CR1;
- and
- R1 is selected from the group consisting of H and C1-C6 alkyl, wherein the alkyl is optionally substituted with a substituent independently selected from the group consisting of halo, hydroxyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2 and C1-C6 heterocyclic group;
- R2 is selected from the group consisting of H and C1-C6 alkyl;
- R4, R5, R6, R7, and R8 are independently selected from the group consisting of H, halo, SR9, and OR9;
- and
- each R9 is independently selected from the group consisting of hydrogen and C1-C10 alkyl.
7 more elements
A method for preparing a compound of formula I-1, comprising:
- 1) reacting a compound of formula IV with a compound of formula V to obtain a compound of formula III:
- 2) hydrolyzing the compound of formula III to obtain a compound of formula II
- and
- 3) reacting the compound of formula II with O-(2-(vinyloxy)ethyl)hydroxylamine, followed by hydrolysis to obtain the compound of formula I-1,
- wherein Ra and Rb are each independently selected from the group consisting of hydrogen and C1-C6 alkyl;
- represents X—Y═W or X═Y—W;
- X and W are independently selected from the group consisting of N, O, S, and CR2;
- Y is CR1;
- and
- R1 is selected from the group consisting of H and C1-C6 alkyl, wherein the alkyl is optionally substituted with a substituent independently selected from the group consisting of halo, hydroxyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2 and C1-C6 heterocyclic group;
- R2 is selected from the group consisting of H and C1-C6 alkyl;
- R4, R5, R6, R7, and R8 are independently selected from the group consisting of H, halo, SR9, and OR9;
- and
- each R9 is independently selected from the group consisting of hydrogen and C1-C10 alkyl.
11 more elements
A method for preparing a compound of formula I-1, comprising:
- a) reacting a compound of formula IV with a compound of formula V to obtain a compound of formula III:
- and
- b) reacting the compound of formula III with O-(2-(vinyloxy)ethyl)hydroxylamine, followed by hydrolysis to obtain the compound of formula I-1,
- wherein Ra and Rb are each independently selected from the group consisting of hydrogen and C1-C6 alkyl;
- represents X—Y═W or X═Y—W;
- X and W are independently selected from the group consisting of N, O, S, and CR2;
- Y is CR1;
- and
- R1 is selected from the group consisting of H and C1-C6 alkyl, wherein the alkyl is optionally substituted with a substituent independently selected from the group consisting of halo, hydroxyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2 and C1-C6 heterocyclic group;
- R2 is selected from the group consisting of H and C1-C6 alkyl;
- R4, R5, R6, R7, and R8 are independently selected from the group consisting of H, halo, SR9, and OR9;
- and
- each R9 is independently selected from the group consisting of hydrogen and C1-C10 alkyl.
10 more elements
Dependencies are inferred from the claim text.