KF-72926
Chemical Name: 2-Cyclopentyl-4-propyl-8(R)-(pyridin-4-ylmethyl)-4,5,7,8-tetrahydro-1H-imidazo[2,1-i]purin-5-one D-tartrate
CAS No. 349554-69-4, 348165-49-1 (free base)
项目整合开发状态: Preclinical
项目研究机构: Kyowa Hakko (Originator)
合成路线:N-Boc-L-(4-Pyridyl)alanine (I) is deprotected and esterified by means of a methanolic solution of SOCl2 to produce amino ester (II).Subsequent acylation of (II) with benzoyl chloride affords benzamide (III).Ester group reduction in (III) by means of NaBH4 yields alcohol (IV).The amide function of (IV) is then hydrolyzed under acidic conditions to furnish (S)-2-amino-3-(4-pyridyl)-1-propanol (V).Coupling of amino alcohol (V) with the known 6-(methylthio)purine (VI) in hot pyridine leads to adduct (VII).Intramolecular cyclization of the purine alcohol (VII) employing thionyl chloride produces the target tricyclic compound,which is finally isolated as the corresponding D-tartrate salt.
合成路线:In a related method,the purine thioether (I) is oxidized to sulfone (II) by means of oxone under phase-transfer conditions.Coupling of sulfone (II) with the pyridyl amino alcohol (III) yields adduct (IV),which is finally cyclized to the target tricyclic compound upon treatment with thionyl chloride.
📌 参考资料/链接：
参考文献标题:Fused purine derivs.
文献作者:Nomoto,Y.; Nakanishi,S.; Ohta,Y.; Ogawa,A.; Suzuki,C.; Ueno,K.; Yano,H.; Kusaka,H.; Takasaki,K.(Kyowa Hakko Kogyo Co.,Ltd.)
参考来源:EP 1251130; WO 0147931
📄 详细内容
合成路线:N-Boc-L-(4-Pyridyl)alanine (I) is deprotected and esterified by means of a methanolic solution of SOCl2 to produce amino ester (II).Subsequent acylation of (II) with benzoyl chloride affords benzamide (III).Ester group reduction in (III) by means of NaBH4 yields alcohol (IV).The amide function of (IV) is then hydrolyzed under acidic conditions to furnish (S)-2-amino-3-(4-pyridyl)-1-propanol (V).Coupling of amino alcohol (V) with the known 6-(methylthio)purine (VI) in hot pyridine leads to adduct (VII).Intramolecular cyclization of the purine alcohol (VII) employing thionyl chloride produces the target tricyclic compound,which is finally isolated as the corresponding D-tartrate salt.
参考文献标题:A new class of antidiabetic drugs; insulin secretion potentiator: Synthesis and biological activity of imidazopurine derivatives
文献作者:Ueno,K.; et al.
参考来源:22nd Symp Med Chem (Nov 27 2002,Shizuoka) 2002,Abst 2P-05