Synthesis of Substituted Thienopyrimidine-4-ones

Abstract

The parallel solution-phase synthesis of more than 3000 substituted thienopyrimidin-4-ones has been accomplished. Key reactions include assembly of the 2-thioxopyrimidin-4-one ring by condensation of isomeric aminothiophenecarboxylates or their appropriate reactive derivatives (isothiocyanates or dithiocarbamates) with the corresponding isothiocyanates or amines. The libraries from libraries were then obtained in good yields and purities using solution-phase alkylation and acylation methodologies. Simple manual techniques for parallel reactions using special CombiSyn synthesizers were coupled with easy purification procedures (crystallization from the reaction mixtures) to give high-purity final products. The scope and limitations of the developed approach are discussed.

Synthesis of Thienopyrimidine Derivatives Starting From Thiophene Ring and Pyrimidine Ring

“…11 The attempts to obtain 3-(2-chloroethyl)thieno[3,2-d]pyrimidine-2,4(1H, 3H)-dione (26) led to a very slow reaction. In more complicated conditions (two-days boiling ammonia-dioxane solution) led to a tricyclic compound in 78 % yield (27) (Scheme 8).…”

“…Thiophene amino esters (10) were reacted with 2-chloroethyl isocyanate in toluene and gave the 4-(2-chloroethyl)thiophene derivatives (11). Compounds (11) were then reacted with 2-methoxyphenylpiperazines in THF, 2-propanol or DMF to afford the thienopyrimidine-2,4-dione derivatives in 56 % yield (12) (Scheme 3).…”

“…Compounds (11) were then reacted with 2-methoxyphenylpiperazines in THF, 2-propanol or DMF to afford the thienopyrimidine-2,4-dione derivatives in 56 % yield (12) (Scheme 3).…”

Development of thieno- and benzopyrimidinone inhibitors of the Hedgehog signaling pathway reveals PDE4-dependent and PDE4-independent mechanisms of action

“…In most cases, formation of the dithiourea 7 32 was followed by two-step cyclization with primary amines to yield the cyclic thiourea 8 ; however, on smaller scales, direct formation of thioureas with isothiocyanates and subsequent cyclization also arrived at 8 . 33 S -alkylation under mild conditions installed alkyl ketones to provide EGM1 analogs 9a – n and tetrahydropyran and tetrahydrothiopyran analogs 9o and 9p . In the case of Y = NBoc, further Boc deprotection gave piperidine 10a .…”

Sequential One-Pot Synthesis of 5,6,8-Trihydropyrano[3',4':4,5]thieno[2,3-d]pyrimidin-4(3H)-one

“…因此, 噻吩并嘧啶酮及其衍生物的研 究日益引起人们的关注. 噻吩并嘧啶酮的合成可采用烯 胺脂与异硫氰酸脂反应 [8] 、分子内邻酰基化反应 [9] 、 Thio-Claisen 重排 [10] 、烯胺脂和酰氯及亚胺反应 [11] 所用试剂为分析纯. 其中乙腈、三乙胺用 4 Å 分子 筛干燥后重蒸; 四氢呋喃用金属钠和二苯甲酮回流后重 蒸.…”