N-phenyl-N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]amine; N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]aniline -Drug Synthesis Database

【结构式】

【分子编号】37038

【品名】N-phenyl-N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]amine; N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]aniline

【CA登记号】

【分子式】C₁₆H₂₄N₂

【分子量】244.38004

【元素组成】C 78.64% H 9.9% N 11.46%

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：(VI)

This compound can be obtained by three different ways: 1) The reaction of 1-(p-chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetic acid (indomethacin) (I) with SOCl2 gives the corresponding acetyl chloride (II), which is treated with hydroxylamine hydrochloride and NaOH in water to afford 1-(p-chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetohydroxamic acid (III). Finally, this compound is hydrolyzed with 0.5 N NaOH in water. 2) The reaction of 1-(p-chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetal-dehyde (IV) with N-hydroxybenzenesulfonamide (V) in DMSO by means of NaOH yields compound (III) already obtained. 3) By reaction of tert-butyl-5-methoxy-2-methyl-3-indolylacetate (VI) with hydroxylamine in methanol.

参考文献中间体

合成目标

【1】 Tamietto, T.; Franzone, J.S.; De Martiis, F.; Sintesi e proprieta ntiflogistiche di alcuni acidi acetoidrossamici. Boll Chim Farm 1975, 114, 309-318.
【2】 De Martiis, F.; Arrigoni-Martelli, E.; Tamietto, T.; US 3624103 .
【3】 Tamietto, T.; US 4186133 .
【4】 Serradell, M.N.; de Angelis, L.; Blancafort, P.; Castaner, J.; ABC-8/5. Drugs Fut 1982, 7, 6, 371.

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)	22930	2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid		C₁₉H₁₆ClNO₄	详情	详情
(II)	24047	2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetyl chloride		C₁₉H₁₅Cl₂NO₃	详情	详情
(III)	37034	2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N-hydroxyacetamide		C₁₉H₁₇ClN₂O₄	详情	详情
(IV)	37035	2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetaldehyde		C₁₉H₁₆ClNO₃	详情	详情
(V)	37036	N-hydroxybenzenesulfonamide	599-71-3	C₆H₇NO₃S	详情	详情
(VI)	37038	N-phenyl-N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]amine; N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]aniline		C₁₆H₂₄N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The condensation of cyclohexene-epoxide (I) with pyrrolidine (II) gives trans-2-(1-pyrrolidinyl)cyclohexanol (III), which by reaction with NaH and methanesulfonyl chloride, and then with benzylamine is converted into trans-2-(1-pyrrolidinyl)-N-benzylcyclohexylamine (IV). The debenzylation of (IV) by hydrogenolysis with H2 over Pd/C affords trans-2-(1-pyrrolidinyl)cyclohexylamine (V), which is formylated with ethyl formate to the corresponding N-formyl-trans-2-(1-pyrrolidinyl)cyclohexylamine (VI). The reduction of (VI) with LiAlH4 in refluxing ether gives trans-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine (VII), which is finally condensed with 3,4-dichlorophenylacetic acid (VIII) by means of carbonyl diimidazole (IX) in THF.

参考文献中间体

合成目标

【1】 Blancafort, P.; Castaner, J.; Serradell, M.N.; U-50488. Drugs Fut 1982, 7, 6, 416.
【2】 Szmuszkovicz, J.; 2-Aminocycloaliphatic amide compounds. DE 2749950; ES 463876; FR 2370723; GB 1569225; JP 53063351; JP 61233654; US 4145435 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	15147	Benzylamine; Phenylmethanamine	100-46-9	C₇H₉N	详情	详情
(B)	16602	ethyl formate	109-94-4	C₃H₆O₂	详情	详情
(I)	17986	7-oxabicyclo[4.1.0]heptane; cyclohexene oxide	286-20-4	C₆H₁₀O	详情	详情
(II)	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情
(III)	14637	(1R,2R)-2-(1-pyrrolidinyl)cyclohexanol		C₁₀H₁₉NO	详情	详情
(IV)	37038	N-phenyl-N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]amine; N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]aniline		C₁₆H₂₄N₂	详情	详情
(V)	37040	(1R,2R)-2-(1-pyrrolidinyl)cyclohexylamine; (1R,2R)-2-(1-pyrrolidinyl)cyclohexanamine		C₁₀H₂₀N₂	详情	详情
(VI)	37011	1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-quinoxalinyl)-2-propen-1-one		C₁₅H₂₀N₂O	详情	详情
(VII)	31357	N-methyl-N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]amine; (1R,2R)-N-methyl-2-(1-pyrrolidinyl)cyclohexanamine		C₁₁H₂₂N₂	详情	详情
(VIII)	30414	2-(3,4-dichlorophenyl)acetic acid；2-(3,4-Dichlorophenyl)acetic acid	5807-30-7	C₈H₆Cl₂O₂	详情	详情
(IX)	11353	1,1'-Carbonyldiimidazole; Di(1H-imidazol-1-yl)methanone; N,N-Carbonyldiimidazole; 1,1'-Carbonylbis(1H-imidazole)	530-62-1	C₇H₆N₄O	详情	详情
(X)	37039	7-azabicyclo[4.1.0]heptane		C₆H₁₁N	详情	详情

Extended Information