【结 构 式】 |
【分子编号】45362 【品名】2,3,4,5,6-pentamethylbenzyl 4-fluorocyclohexanecarboxylate 【CA登记号】 |
【 分 子 式 】C19H27FO2 【 分 子 量 】306.4205832 【元素组成】C 74.48% H 8.88% F 6.2% O 10.44% |
合成路线1
该中间体在本合成路线中的序号:(VII)A mixture of cis and trans 4-hydroxycyclohexanecarboxylic acids (II), obtained by basic hydrolysis of the corresponding ethyl ester (I), was alkylated with pentamethylbenzyl chloride (III) in the presence of Et3N to afford pentamethylbenzyl ester (IV). Recrystallization from methylene chloride/hexane provided pure cis isomer, which was converted to 4-nitrobenzenesulfonate (VI) with p-nitrobenzenesulfonyl chloride (V) and Et3N. Subsequent displacement of the sulfonate group of (VI) for a 18F- provided the labeled intermediate (VII). Then, cleavage of the benzyl ester of (VII) with trifluoroacetic acid, followed by treatment with dichloromethyl methyl ether gave trans 4-18fluorocyclohexanecarbonyl chloride (VIII). This was finally coupled with amine (WAY-100634)(IX) in the presence of Et3N in CH2Cl2 to produce the target amide.
【1】 Mitchell, M.A.; Hendges, S.K.; Jacobsen, E.J.; et al.; Synthesis of a series of stromelysin-selective thiadiazole urea matrix metalloproteinase inhibitors. J Med Chem 1999, 42, 9, 1525. |
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) | 24656 | ethyl 4-hydroxycyclohexanecarboxylate | C9H16O3 | 详情 | 详情 | |
(II) | 24657 | 4-hydroxycyclohexanecarboxylic acid | 17419-81-7 | C7H12O3 | 详情 | 详情 |
(III) | 24649 | 1-(chloromethyl)-2,3,4,5,6-pentamethylbenzene | 484-65-1 | C12H17Cl | 详情 | 详情 |
(IV) | 24659 | 2,3,4,5,6-pentamethylbenzyl 4-hydroxycyclohexanecarboxylate | C19H28O3 | 详情 | 详情 | |
(V) | 15809 | 4-nitrobenzenesulfonyl chloride | 98-74-8 | C6H4ClNO4S | 详情 | 详情 |
(VI) | 24661 | 2,3,4,5,6-pentamethylbenzyl 4-[[(4-nitrophenyl)sulfonyl]oxy]cyclohexanecarboxylate | C25H31NO7S | 详情 | 详情 | |
(VII) | 24662 | 2,3,4,5,6-pentamethylbenzyl 4-fluorocyclohexanecarboxylate | C19H27FO2 | 详情 | 详情 | |
(VII) | 45362 | 2,3,4,5,6-pentamethylbenzyl 4-fluorocyclohexanecarboxylate | C19H27FO2 | 详情 | 详情 | |
(VIII) | 24663 | 4-fluorocyclohexanecarbonyl chloride | C7H10ClFO | 详情 | 详情 | |
(VIII) | 45363 | 4-fluorocyclohexanecarbonyl chloride | C7H10ClFO | 详情 | 详情 | |
(IX) | 24655 | N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-2-pyridinamine | C18H24N4O | 详情 | 详情 |