【结 构 式】 |
【分子编号】29011 【品名】6-(2-bromoethyl)-7-methyl-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one 【CA登记号】 |
【 分 子 式 】C9H11BrN2OS 【 分 子 量 】275.16922 【元素组成】C 39.28% H 4.03% Br 29.04% N 10.18% O 5.81% S 11.65% |
合成路线1
该中间体在本合成路线中的序号:(IV)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).
【1】 Kennis, L.; Mertens, J.C. (Janssen Pharmaceutica NV); Bicyclic pyrimidin-5-one derivatives. DD 215553; EP 0070053; US 4443451 . |
【2】 Serradell, M.N.; Castaner, J.; Setoperone. Drugs Fut 1985, 10, 1, 40. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 29009 | 5-(2-hydroxyethyl)-6-methyl-2-sulfanyl-4-pyrimidinol | C7H10N2O2S | 详情 | 详情 | |
(II) | 10252 | 1,2-Dibromoethane; Ethylene dibromide | 106-93-4 | C2H4Br2 | 详情 | 详情 |
(III) | 29010 | 6-(2-hydroxyethyl)-7-methyl-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one | C9H12N2O2S | 详情 | 详情 | |
(IV) | 29011 | 6-(2-bromoethyl)-7-methyl-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one | C9H11BrN2OS | 详情 | 详情 | |
(V) | 29012 | 1-bromo-4-fluorobenzene | 460-00-4 | C6H4BrF | 详情 | 详情 |
(VI) | 29013 | 1-benzyl-4-piperidinecarbonitrile | C13H16N2 | 详情 | 详情 | |
(VII) | 29014 | (1-benzyl-4-piperidinyl)(4-fluorophenyl)methanone | C19H20FNO | 详情 | 详情 | |
(VIII) | 29015 | ethyl 4-(4-fluorobenzoyl)-1-piperidinecarboxylate | C15H18FNO3 | 详情 | 详情 | |
(IX) | 21497 | (4-Fluorophenyl)(4-piperidinyl)methanone; 4-(4-Fluorobenzoyl)piperidine; 4-(p-Fluorobenzoyl)piperidine | 56346-57-7 | C12H14FNO | 详情 | 详情 |