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【结 构 式】 
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【分子编号】26030 【品名】5-iodo-2,6-dimethyl-4-pyrimidinol 【CA登记号】 |
【 分 子 式 】C6H7IN2O 【 分 子 量 】250.03893 【元素组成】C 28.82% H 2.82% I 50.75% N 11.2% O 6.4% |
合成路线1
该中间体在本合成路线中的序号：(X)3) The iodination of 2,6-dimethylpyrimidin-4-ol (IX) with I2/NaOH in refluxing water gives 5-iodo-2,6-dimethylpyrimidin-4-ol (X), which is treated with POCl3 in refluxig toluene yielding 4-chloro-5-iodo-2,6-dimethylpyrimidine (XI). The reaction of (XI) with (1-ethoxyvinyl)tributyltin (XII) catalyzed by tetrakis(triphenylphosphine)palladium in refluxing dioxane affords 4-chloro-5-(1-ethoxyvinyl)-2,6-dimethylpyrimidine (XIII), which is condensed with 4-bromobenzylamine (XIV) by means of NaHCO3 in refluxing butanol giving 4-(4-bromobenzylamino)-5-(1-ethoxyvinyl)-2,6-dimethylpyrimidine (XV). The hydrolysis of (XV) with HCl in refluxing acetone yields the corresponding acetyl derivative (XVI), which is condensed with 2-(2-tert-butyl-2H-tetrazol-5-yl)phenylboronic acid (XVII) by means of tetrakis(triphenylphosphine)palladium to afford the biphenyl derivative (XVIII). The cyclization of (XVIII) with diethyl carbonate and NaH in hot THF gives 8-[2'-(2-tert-butyl-2H-tetrazol-5-yl)biphenyl-4-ylmethyl]-5-hydroxy-2,4-dimethylpyrido[2,3-d]pyrimidin-7(8H)-one (XIX), which is finally deprotected with trifluoromethanesulfonic acid in refluxing toluene to give metabolite (III).
| 【1】 Ellingboe, J.W.; Collini, M.D.; Quagliato, D.; Chen, J.; Antane, M.; Schmid, J.; Hartupee, D.; White, V.; Park, C.H.; Tanikella, T.; Bagli, J.F.; Metabolites of the angiotensin II antagonist tasosartan: The importance of a second acidic group. J Med Chem 1998, 41, 22, 4251. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 26028 | 5-hydroxy-2,4-dimethyl-8-[[2'-(1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]pyrido[2,3-d]pyrimidin-7(8H)-one | C23H19N7O2 | 详情 | 详情 | |
| (IX) | 26029 | 2,6-dimethyl-4-pyrimidinol | 6622-92-0 | C6H8N2O | 详情 | 详情 |
| (X) | 26030 | 5-iodo-2,6-dimethyl-4-pyrimidinol | C6H7IN2O | 详情 | 详情 | |
| (XI) | 26031 | 4-chloro-5-iodo-2,6-dimethylpyrimidine | C6H6ClIN2 | 详情 | 详情 | |
| (XII) | 19760 | ethyl 1-(tributylstannyl)vinyl ether; tributyl(1-ethoxyvinyl)stannane | 97674-02-7 | C16H34OSn | 详情 | 详情 |
| (XIII) | 26032 | 1-(4-chloro-2,6-dimethyl-5-pyrimidinyl)vinyl ethyl ether; 4-chloro-5-(1-ethoxyvinyl)-2,6-dimethylpyrimidine | C10H13ClN2O | 详情 | 详情 | |
| (XIV) | 15869 | 4-bromobenzylamine; (4-bromophenyl)methanamine | 26177-44-6 | C7H8BrN | 详情 | 详情 |
| (XV) | 26033 | N-(4-bromobenzyl)-5-(1-ethoxyvinyl)-2,6-dimethyl-4-pyrimidinamine; N-(4-bromobenzyl)-N-[5-(1-ethoxyvinyl)-2,6-dimethyl-4-pyrimidinyl]amine | C17H20BrN3O | 详情 | 详情 | |
| (XVI) | 26034 | 1-[4-[(4-bromobenzyl)amino]-2,6-dimethyl-5-pyrimidinyl]-1-ethanone | C15H16BrN3O | 详情 | 详情 | |
| (XVII) | 15871 | 2-[2-(tert-butyl)-2H-1,2,3,4-tetraazol-5-yl]phenylboronic acid | C11H15BN4O2 | 详情 | 详情 | |
| (XVIII) | 26035 | 1-[4-[([2'-[2-(tert-butyl)-2H-1,2,3,4-tetraazol-5-yl][1,1'-biphenyl]-4-yl]methyl)amino]-2,6-dimethyl-5-pyrimidinyl]-1-ethanone | C26H29N7O | 详情 | 详情 | |
| (XIX) | 26036 | 8-([2'-[2-(tert-butyl)-2H-1,2,3,4-tetraazol-5-yl][1,1'-biphenyl]-4-yl]methyl)-5-hydroxy-2,4-dimethylpyrido[2,3-d]pyrimidin-7(8H)-one | C27H27N7O2 | 详情 | 详情 |