1-(chloromethyl)-2,3,4,5,6-pentamethylbenzene -Drug Synthesis Database

【结构式】

【分子编号】24649

【品名】1-(chloromethyl)-2,3,4,5,6-pentamethylbenzene

【CA登记号】484-65-1

【分子式】C₁₂H₁₇Cl

【分子量】196.71968

【元素组成】C 73.27% H 8.71% Cl 18.02%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(II)

Condensation of 4-(dimethylamino)-3-methylbenzoic acid (I) with pentamethylbenzyl chloride (II) in the presence of Et3N afforded ester (III). The tertiary amino group of (III) was then methylated using methyl trifluoromethane-sulfonate to provide ammonium salt (IV). Subsequent displacement of the trimethylammonium salt of (IV) for a 18F-, followed by cleavage of the benzyl ester (V) with trifluoroacetic acid, provided the labeled intermediate 4-18fluoro-3-methylbenzoic acid (VI). Treatment of (VI) with dichloromethyl methyl ether gave the corresponding acid chloride (VII), which was finally coupled with amine (WAY 100634)(VIII) to produce the target amide.

参考文献中间体

合成目标

【1】 Lang, L.; et al.; Development of fluorine-18-labeled 5-HT1A antagonists. J Med Chem 1999, 42, 9, 1576.

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)	24648	4-(dimethylamino)-3-methylbenzoic acid		C₁₀H₁₃NO₂	详情	详情
(II)	24649	1-(chloromethyl)-2,3,4,5,6-pentamethylbenzene	484-65-1	C₁₂H₁₇Cl	详情	详情
(III)	24650	2,3,4,5,6-pentamethylbenzyl 4-(dimethylamino)-3-methylbenzoate		C₂₂H₂₉NO₂	详情	详情
(IV)	24651	N,N,N,2-tetramethyl-4-[[(2,3,4,5,6-pentamethylbenzyl)oxy]carbonyl]benzenaminium		C₂₃H₃₂NO₂	详情	详情
(V)	24652	2,3,4,5,6-pentamethylbenzyl 4-fluoro-3-methylbenzoate		C₂₀H₂₃FO₂	详情	详情
(V)	45359	2,3,4,5,6-pentamethylbenzyl 4-fluoro-3-methylbenzoate		C₂₀H₂₃FO₂	详情	详情
(VI)	24653	4-fluoro-3-methylbenzoic acid		C₈H₇FO₂	详情	详情
(VI)	45360	4-fluoro-3-methylbenzoic acid		C₈H₇FO₂	详情	详情
(VII)	24654	4-fluoro-3-methylbenzoyl chloride		C₈H₆ClFO	详情	详情
(VII)	45361	4-fluoro-3-methylbenzoyl chloride		C₈H₆ClFO	详情	详情
(VIII)	24655	N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-2-pyridinamine		C₁₈H₂₄N₄O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

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.

参考文献中间体

合成目标

【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

Extended Information