637031-93-7Relevant articles and documents
3, 3-difluorocyclobutylamine hydrochloride intermediate, synthetic method thereof and synthetic method of 3, 3-difluorocyclobutylamine hydrochloride
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Paragraph 0034; 0062-0065, (2021/01/30)
The invention relates to a 3, 3-difluorocyclobutylamine hydrochloride intermediate, a synthetic method thereof and a synthetic method of 3, 3-difluorocyclobutylamine hydrochloride. The method comprises the following steps: generating a methyl ester compound from 3-oxo cyclobutanecarboxylic acid under acid catalysis, fluorinating the methyl ester compound to obtain a fluoride, and reacting with hydroxylamine to generate the 3, 3-difluorocyclobutylamine hydrochloride intermediate, subjecting the 3, 3-difluorocyclobutylamine hydrochloride intermediate torearrangement reaction under the action ofsulfonyl chloride and alkali without purification and separation to obtain 3, 3-difluorocyclobutylamine, and finally salifying 3, 3-difluorocyclobutylamine and hydrochloric acid to generate 3, 3-difluorocyclobutylamine hydrochloride. The synthetic method of the 3, 3-difluorocyclobutylamine hydrochloride does not need to use azide, is mild in reaction condition, safe and environment-friendly, is simple in process route, remarkably shortens the production period, has advantages in productivity, and is simple and easily available in raw materials, low in cost and suitable for industrial mass production.
Preparation method of ivosidenib intermediate 3,3-difluorocyclobutanamine hydrochloride
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Paragraph 0048-0055, (2019/04/10)
The invention belongs to the technical field of medicine, and specifically relates to a preparation method of 3,3-difluorocyclobutanamine hydrochloride (I). The preparation method comprises the following steps: amidating a compound II, thus obtaining a compound III; reacting with a fluorinated reagent, thus obtaining a compound IV; then carrying out Hofman degradation reaction, thus obtaining a compound V; finally salifying, thus obtaining the 3,3-difluorocyclobutanamine hydrochloride (I). Compared with the prior art, the technical route is simple, the steps are shorter, the cost is low, the reaction condition is gentle, reagents which are toxic and are high in danger coefficient are prevented from being used, the preparation method is green and environmentally friendly, and good application value is obtained.
Lead Optimization toward Proof-of-Concept Tools for Huntington's Disease within a 4-(1 H -Pyrazol-4-yl)pyrimidine Class of Pan-JNK Inhibitors
Wityak, John,McGee, Kevin F.,Conlon, Michael P.,Song, Ren Hua,Duffy, Bryan C.,Clayton, Brent,Lynch, Michael,Wang, Gwen,Freeman, Emily,Haber, James,Kitchen, Douglas B.,Manning, David D.,Ismail, Jiffry,Khmelnitsky, Yuri,Michels, Peter,Webster, Jeff,Irigoyen, MacArena,Luche, Michele,Hultman, Monica,Bai, Mei,Kuok, Iokteng D.,Newell, Ryan,Lamers, Marieke,Leonard, Philip,Yates, Dawn,Matthews, Kim,Ongeri, Lynette,Clifton, Steve,Mead, Tania,Deupree, Susan,Wheelan, Pat,Lyons, Kathy,Wilson, Claire,Kiselyov, Alex,Toledo-Sherman, Leticia,Beconi, Maria,Mu?oz-Sanjuan, Ignacio,Bard, Jonathan,Dominguez, Celia
, p. 2967 - 2987 (2015/04/27)
Through medicinal chemistry lead optimization studies focused on calculated properties and guided by X-ray crystallography and computational modeling, potent pan-JNK inhibitors were identified that showed submicromolar activity in a cellular assay. Using in vitro ADME profiling data, 9t was identified as possessing favorable permeability and a low potential for efflux, but it was rapidly cleared in liver microsomal incubations. In a mouse pharmacokinetics study, compound 9t was brain-penetrant after oral dosing, but exposure was limited by high plasma clearance. Brain exposure at a level expected to support modulation of a pharmacodynamic marker in mouse was achieved when the compound was coadministered with the pan-cytochrome P450 inhibitor 1-aminobenzotriazole. (Chemical Presented)