- A practical chromatography-free synthesis of a 5,6-dihydroimidazolo[1,5-f]pteridine derivative as a polo-like kinase-1 inhibitor
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A practical chromatography-free synthesis of a potent polo-like kinase-1 inhibitor possessing a unique 5,6-dihydroimidazolo[1,5-f]pteridine structure has been developed. We showed that key cyanoimidazole ring formation could be conducted at benign temperature and obtained a chiral 5,6-dihydroimidazolo[1,5-f]pteridine derivative in good yield without epimerization. An aniline derivative containing a trans 1,4-cyclohexyl diamine structure was prepared by a synthesis that makes use of defined stereocenters of commercially available trans-cyclohexane-1,4-diamine via selective piperazine ring formation from a primary diamine. A coupling reaction of the 3-chloro-5,6-dihydroimidazolo[1,5-f]pteridine derivative and the aniline derivative in the endgame was closely investigated, and good yields were achieved both by palladium-catalyzed amination and acid-promoted coupling under benign reaction conditions. As a result of these investigations, the polo-like kinase-1 inhibitor was successfully obtained in a practical way without concern for generation/separation of stereoisomers.
- Ishimoto, Kazuhisa,Nakaoka, Keiichiro,Yabe, Osamu,Nishiguchi, Atsuko,Ikemoto, Tomomi
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p. 5779 - 5790
(2018/08/25)
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- CRYSTALLINE FORM OF A DIHYDROPTERIDIONE DERIVATIVE
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The present invention relates to a crystalline form a dihydropteridione derivative, namely a crystalline form of the free base N- [trans-4- [4- (cyclopropylmethyl) - 1-piperazinyl] cyclohexyl] -4- [[(7R) -7-ethyl-5, 6. 7, 8 - tetrahydro - 5 -methyl - 8 -
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Page/Page column 12
(2009/04/25)
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- TRIHYDROCHLORIDE FORMS OF A DIHYDROPTERIDINONE DERIVATIVE AND PROCESSES FOR PREPARATION
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The present invention relates to a specific salt of a dihydropteridione derivative, namely the trihydrochloride salt of the compound N-[trans-4-[4-(cyclopropylmethyl)-1- piperazinyl]cyclohexyl]-4-[[(7R)-7-ethyl-5,6,7,8-tetrahydro-5-methyl-8-(1-methylethyl
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Page/Page column 12
(2008/06/13)
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