Setoperone(Rec INN, USAN), R-52245

噻托哌隆Chemical Name: 6-[2-[4-(4-Fluorobenzoyl)piperidino]ethyl]-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one
CAS No. 86487-64-1
项目整合开发状态: Biological Testing
项目研究机构: Janssen (Originator)
合成路线:By condensation of 4-(4-fluorobenzoyl)piperidine (IX) with 6-(2-bromo ethyl)-7-methyl-2,3-dihydro-5H-thiazolo[2,3-a]pyrimidin-5-one (IV) by means of Na2CO3 in refluxing 4-methyl-2-pentanone.The starting products are obtained as follows: The cyclization of 4-hydroxy-5-(2-hydroxyethyl)-6-methyl-2-mercaptopyrimidine (I) with 1,2-dibromo ethane (II) by means of K2CO3 in hot dimethylacetamide gives 2,3-dihydro-6-(2-hydroxyethyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one (II),which by reaction with HBr in refluxing acetic acid is converted to the corresponding 6-(2-bromoethyl) derivative (IV).The Grignard reaction of 4-bromofluorobenzene (V) with N benzyl-4 cyanopiperidine (VI) by means of Mg in dimethoxyethane gives 4-(4-fluorobenzoyl)-N-benzylpiperidine (VII),which is treated with ethyl chlorocarbo-nate in refluxing toluene to afford ethyl 4-(4-fluorobenzoyl)piperidine-1-carboxylate (VIII).Finally,this compound is treated with HBr in refluxing 48% HBr to give (IX).