KF-21213

8-[(E)-2-(2,3-二甲基-4-甲氧苯基)乙烯基]-1,3,7-三甲基-3,7-二氢-1H-嘌呤-2,6-二酮Chemical Name: 8-[(E)-2-(2,3-Dimethyl-4-methoxyphenyl)vinyl]-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione
CAS No. 155271-17-3
项目整合开发状态: Preclinical
项目研究机构: Kyowa Hakko (Originator)
合成路线:Cyclization of N,N'-diethylurea (I) with cyanoacetic acid (II) in hot acetic anhydride gives 6-amino-1,3-diethyluracil (III) which is nitrosated with NaNO2/HOAc in water to yield 6-amino-1,3-diethyl-5-nitrosouracil (IV).The reduction of (IV) with Na2S2O4 and K2CO3 in concentrated aqueous ammonia affords 5,6-diamino-1,3-diethyluracil (V),which is condensed with either 3-(3,4-dimethoxyphenyl)-2(E)-propenoyl chloride (VI) in EtOH/water or 3-(3,4-dimethoxyphenyl)-2(E)-propenoic acid (VII) and 3-[3-(diethylamino)propyl]-1-ethylcarbodiimide (EDAC) in dioxane/water to provide the corresponding amide (VIII).Cyclization of (VIII) by means of NaOH in the same solvent furnishes the xanthine derivative (IX),which is finally methylated with methyl iodide and K2CO3 in DMF.

合成路线:Acylation of 5,6-diamino-1,3-dimethyluracil (I) with 4-methoxy-2,3-dimethylcinnamic acid (II) in the presence of EDC gave amide (III).This was then cyclized under basic conditions to afford the styryltheophylline derivative (IV).Finally,methylation of (IV) with iodomethane and K2CO3 furnished the title caffeine derivative.