1-adamantanecarbonyl chloride -Drug Synthesis Database

【结构式】

【分子编号】31216

【品名】1-adamantanecarbonyl chloride

【CA登记号】2094-72-6

【分子式】C₁₁H₁₅ClO

【分子量】198.6922

【元素组成】C 66.5% H 7.61% Cl 17.84% O 8.05%

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：(I)

Adamantane-1-carboxylic acid chloride (freshly prepared from the reaction of thionyl chloride (I) with the adamantane-1-carboxylic acid) was reacted with 1-(2-aminoethyl)-4-(2-pyrimidinyl)piperazine (II) in CH2Cl2 in the presence of triethylamine (TEA) to afford Wy-50,324 free base in 70% (III) yield which was converted to the hydrochloride salt using ethanolic HCl solution.

参考文献中间体

合成目标

【1】 Abou-Gharbia, M.A.; et al.; Synthesis and SAR of adatanserin: Novel adamantyl aryl- and heteroarylpiperazines with dual serotonin 5-HT1A and activity as potential anxiolytic and antidepressant agents. J Med Chem 1999, 42, 25, 5077.
【2】 Abou-Gharbia, M.A.-M.; Yardley, J.P.; Childers, W.E. Jr. (American Home Products Corp.); Aryl- and heteroaryl piperazinyl carboxamides having CNS activity. AU 8935025; EP 0343961; JP 1990015059 .
【3】 Abou-Gharbia, M.; Moyer, J.A.; Wy-50,324. Drugs Fut 1990, 15, 11, 1093.

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)	31216	1-adamantanecarbonyl chloride	2094-72-6	C₁₁H₁₅ClO	详情	详情
(II)	31217	2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylamine; 2-[4-(2-pyrimidinyl)-1-piperazinyl]-1-ethanamine		C₁₀H₁₇N₅	详情	详情
(III)	31218	N-[2-[4-(2-pyrimidinyl)-1-piperazinyl]ethyl]-1-adamantanecarboxamide		C₂₁H₃₁N₅O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Condensation of (S)-3-amino-1-benzylpyrrolidine (I) with 1-adamantanecarbonyl chloride (II) by means of Et3N in dichloromethane affords amide (III), which is then debenzylated by hydrogenolysis over Pd/C and hydrazine monohydrate to provide amine (IV). Subsequent N-alkylation of (IV) with tosylate (V) in acetonitrile in the presence of K2CO3 furnishes the corresponding alylated compound (VI), which is finally converted into the desired hydrochloride monohydrate derivative by first treatment with HCl:isopropanol in ethyl acetate followed by recrystallization in EtOH:H2O using activated carbon.

参考文献中间体

合成目标

【1】 Kuroita, T.; Sakai, Y.; Fujio, M.; Nakagawa, H.; Matsumoto, Y.; N-[1-(2-phenylethyl)pyrrolidin-3-yl]-1-adamantanecarboxamides as novel 5-HT2 receptor antagonists. Bioorg Med Chem Lett 2000, 10, 21, 2457.
【2】 Kuroita, T.; Nakagawa, H.; Fujio, M. (Welfide Corporation); Pyrrolidine cpds. and medicinal utilization thereof. EP 1125922; WO 0026186 .

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)	48990	(S)-N-Benzyl-3-aminopyrrolidine; (3S)-(+)-1-Benzyl-3-aminopyrrolidine; (3S)-(+)-N-Benzyl-3-amino pyrrolidine	114715-38-7	C₁₁H₁₆N₂	详情	详情
(II)	31216	1-adamantanecarbonyl chloride	2094-72-6	C₁₁H₁₅ClO	详情	详情
(III)	48991	N-[(3S)-1-benzylpyrrolidinyl]-1-adamantanecarboxamide		C₂₂H₃₀N₂O	详情	详情
(IV)	48992	N-[(3R)pyrrolidinyl]-1-adamantanecarboxamide		C₁₅H₂₄N₂O	详情	详情
(V)	45818	2-(4-fluorophenyl)-1-ethanamine; 4-fluorophenethylamine		C₈H₁₀FN	详情	详情
(VI)	48993	N-[(3R)-1-(4-fluorophenethyl)pyrrolidinyl]-1-adamantanecarboxamide		C₂₃H₃₁FN₂O	详情	详情

Extended Information