6494-19-5Relevant articles and documents
Preparation method of pazopanib intermediate
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Paragraph 0185-0187; 0192-0193, (2021/03/24)
The invention provides a preparation method of a pazopanib key intermediate 2,3-dimethyl-N-(2-chloropyrimidin-4-yl)-N-methyl-2H-indazole-6-amine. The method comprises the following steps: by taking 6-halogenated-2,3-dimethyl-2H-indazole as a raw material, conducting reacting to obtain N,2,3-trimethyl-2H-indazole-6-amine; and further carrying out a reaction to obtain the 2,3-dimethyl-N-(2-chloropyrimidin-4-yl)-N-methyl-2H-indazole-6-amine. The method has the advantages of short synthesis route, accessible raw materials, low cost, mild reaction conditions, high safety and high yield, and is suitable for industrial mass production.
Method for synthesizing 3-methyl-6-nitro-1H-indazole by microchannel diazo reaction
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Paragraph 0027; 0028; 0029; 0030; 0031-0034, (2019/03/10)
The invention discloses a method for synthesizing 3-methyl-6-nitro-1H-indazole by a microchannel diazo reaction, and belongs to the technical field of synthesis of pharmaceutical intermediates. According to the method, 2-ethyl-5-nitroaniline, acetic acid and an aqueous nitrous acid solution are taken as starting raw materials, and 3-methyl-6-nitro-1H-indazole is synthesized by diazo cyclization ina short time of tens of seconds to a few minutes in a microchannel reactor. The materials are introduced into the microchannel reactor by a metering pump and then are subjected to preheating, mixingand a nitration reaction, and a 3-methyl-6-nitro-1H-indazole product is obtained. The method is simple and safe to operate, efficient continuous production of the 3-methyl-6-nitro-1H-indazole productis realized, and besides, the environmental pollution caused by the method is obviously reduced.
Method for preparing 2, 3-dimethyl-2H-indazole-6-benzylamine hydrochloride
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Paragraph 0029; 0032; 0035-0037; 0040-0042; 0045-0047, (2020/03/14)
The invention discloses a method for preparing 2, 3-dimethyl-2H-indazole-6-benzylamine hydrochloride. The method comprises the steps of reacting a glacial acetic acid solution of tert-butyl nitrite and a glacial acetic acid solution of 5-nitro-2-ethylaniline in a first microreactor to generate 3-methyl-6-nitro-1H-indazole; reacting a homogeneous solution formed by mixing the 3-methyl-6-nitro-1H-indazole and a dimethyl sulfoxide solution of methyl iodide and a dimethyl sulfoxide solution of sodium ethoxide in a second microreactor to generate 2,3-dimethyl-6-nitro-2H-indazole; then reacting withmixed liquor formed by stirring a concentrated hydrochloric acid solution of stannous chloride and ethyl alcohol in a third microreactor to generate the 2, 3-dimethyl-2H-indazole-6-benzylamine hydrochloride. The method provided by the invention has the advantages of less side reaction, high yield, simplification of a complicated multi-step synthesis process, low toxicity and pollution, low production cost, good product quality, environment friendliness, energy saving and high efficiency, and is suitable for industrialized application.
Hydrochloric acid [...] of the method for the preparation of intermediates
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Paragraph 0033; 0034, (2017/01/02)
The invention discloses a preparation method of an intermediate (2,3-dimethyl-N-(2-chloropyrimidine-4-base)-N-methyl-2H-indazole-6-amine) of pazopanib hydrochloride as shown in a formula I. The preparation method comprises the step of performing nucleophilic substitution reaction on a compound III and 2,4-dichloropyrimidine in an organic solvent under the action of alkali, wherein the reaction temperature is 0-160 DEG C. According to the preparation method disclosed by the invention, raw materials are low in price and easy to obtain, and the preparation method is convenient to operate, high in product yield and suitable for industrial large-scale production.
2,3-dimethyl-6-urea -2H-indazoles and its preparation method and application
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Paragraph 0125-0126; 0130-0132, (2016/10/09)
The invention discloses a 2, 3-dimethyl-6-urea-2H-indazole compound shown by the following general formula (I), medicinal salt or a solvent compound thereof, wherein Ar is substituted or unsubstituted phenyl or aromatic matrix. The invention also discloses a preparation method and application of the compound. The compound can regulate signal transduction of tyrosine kinase, inhibit bad cellular proliferation, and particularly has obvious curative effect for tumors.
Pyrimidineamines as angiogenesis modulators
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Paragraph 0157 - 0159, (2015/11/16)
Pyrimidine derivatives, which are useful as VEGFR2 inhibitors are described herein. The described invention also includes methods of making such pyrimidine derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.
Discovery and synthesis of N2,N4-substitued- cycloalkyl[d]pyrimidine-2,4-diamine analogs: The first examples of small-molecular FGFR-1 activator
Li, Bao-Li,Xiao, Fang,Lu, Wen-Chao,Sun, Yu-Yun,Zhu, Jin,Li, Jian
, p. 989 - 994 (2014/08/18)
A series of novel, cycloalkyl-modified pazopanib analogs 2 and 3 were designed and synthesized. Their kinase modulatory effects on FGFR-1, VEGFR-2, PDGFR-β, and c-KIT were evaluated by the caliper mobility shift assay. Introduction of cycloalkyl into the pyrimidine linker of pazopanib almost abolished the four kinases inhibitory potency of compounds 2 and 3, but surprisingly, resulted in good activation effects on FGFR-1. Compounds 3d and 3g showed double-digit, nanomolar, selective activation effects on FGFR-1, and could be classified as first-generation small molecular activators of FGFR-1 kinase.
A novel practical synthesis of pazopanib: An anticancer drug
Mei, Yi Cheng,Yang, Bao Wei,Chen, Wei,Huang, Dan Dan,Li, Ying,Deng, Xin,Liu, Bao Ming,Wang, Jing Jie,Qian, Hai,Huang, Wen Long
experimental part, p. 276 - 279 (2012/08/27)
Abstract: This paper reports a novel approach to synthesize pazopanib. In our synthetic route, the potently mutagenic alkylating agents such as dimethyl sulfate and methyl iodide are avoided. A novel regioselective methylation of the 2- position of 3-methyl-6-nitro-1H-indazole was reported. This novel route is one step shorter than the previously reported route.
DIHYDROPYRIDONE UREAS AS P2X7 MODULATORS
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Page/Page column 54, (2010/07/04)
Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n, R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with the P2X7 purinergic receptor.
2-AMINOQUINAZOLINE DERIVATIVE
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Page/Page column 39-40, (2010/09/17)
An object of the present invention is to provide compounds which are useful as protein kinase inhibitors. Disclosed is a 2-aminoquinazoline derivative represented by the following formula (I): wherein R1 represents a lower alkyl group which may be substituted with a halogen atom, or a halogen atom; R2 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a halogen atom, a hydroxyl group, a substituted or unsubstituted lower alkoxy group, a substituted or unsubstituted amino group, a substituted or unsubstituted acylamino group, a carboxyl group, a lower alkoxycarbonyl group, a carbamoyl group, or a substituted or unsubstituted lower alkylureido group; and X, Y and Z each independently represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a halogen atom, a hydroxyl group, a carboxyl group, a lower alkoxycarbonyl group, a cyano group, a carbamoyl group, a substituted or unsubstituted lower alkoxy group, a substituted or unsubstituted amino group, a substituted or unsubstituted lower alkoxycarbonylamino group, a substituted or unsubstituted lower alkylaminocarbonyl group, a lower alkylsulfonylamino group, a substituted or unsubstituted lower alkylureido group, or a substituted or unsubstituted acylamino group, or X and Y may be combined to form a 5- to 6-membered ring forming a bicyclic fused ring, wherein the 5- to 6-membered ring may optionally have a substituent, provided that when X and Y are not combined to form a fused ring, R2 represents a hydrogen atom and, when X and Y are combined to form a fused ring, a saturated or unsaturated, bicyclic alicyclic or heterocyclic fused ring can be formed.
