N-Ethylcyclohexanamine; N-Ethylcyclohexylamine; Vulkacit HX -Drug Synthesis Database

【结构式】

【分子编号】59245

【品名】N-Ethylcyclohexanamine; N-Ethylcyclohexylamine; Vulkacit HX

【CA登记号】5459-93-8

【分子式】C₈H₁₇N

【分子量】127.22972

【元素组成】C 75.52% H 13.47% N 11.01%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(VI)

Condensation of 3'-chloro-4'-cyclohexylacetophenone (I) with semicarbazide hydrochloride (II) produced the semicarbazone (III). Treatment of (III) with selenium dioxide in HOAc generated the intermediate selenodiazole (IV) which, on further heating, gave rise to the aryl acetylene (V). Cupric chloride-catalyzed Mannich condensation of acetylene (V) with N-ethyl cyclohexylamine (VI) and formaldehyde yielded the propargyl amine (VII). Partial hydrogenation of the triple bond of (VII) using the Lindlar catalyst provided the target (Z)-propenyl amine, which was finally converted to the hydrochloride salt.

参考文献中间体

合成目标

【1】 Breliere, J.-C.; Casellas, P.; Lavastre, S.; Paul, R. (Sanofi-Synthelabo); Benzene derivates, their preparation and pharmaceutical compsns. containing them. EP 0376850; FR 2641276; JP 1991002116; US 5354781 .

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)	59241	1-(3-chloro-4-cyclohexylphenyl)-1-ethanone		C₁₄H₁₇ClO	详情	详情
(II)	23944	1-Hydrazinecarboxamide	563-41-7	CH₅N₃O	详情	详情
(III)	59242	2-[(E)-1-(3-chloro-4-cyclohexylphenyl)ethylidene]-1-hydrazinecarboxamide		C₁₅H₂₀ClN₃O	详情	详情
(IV)	59243	4-(3-chloro-4-cyclohexylphenyl)-1,2,3-selenadiazole		C₁₄H₁₅ClN₂Se	详情	详情
(V)	59244	2-chloro-1-cyclohexyl-4-ethynylbenzene		C₁₄H₁₅Cl	详情	详情
(VI)	59245	N-Ethylcyclohexanamine; N-Ethylcyclohexylamine; Vulkacit HX	5459-93-8	C₈H₁₇N	详情	详情
(VII)	59246	N-[3-(3-chloro-4-cyclohexylphenyl)-2-propynyl]-N-cyclohexyl-N-ethylamine; N-[3-(3-chloro-4-cyclohexylphenyl)-2-propynyl]-N-ethylcyclohexanamine		C₂₃H₃₂ClN	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

A different synthetic strategy was further reported. Fischer esterification of 4-cyclohexylbenzoic acid (VIII) with MeOH and H2SO4, followed by aromatic nitration of the resultant benzoate ester (IX), yielded methyl 4-cyclohexyl-3-nitrobenzoate (X). Nitro group reduction in (X) by transfer hydrogenation provided amine (XI). This was converted to the chloro derivative (XII) by application of a modified Sandmeyer reaction with tert-butyl nitrite and cupric chloride. Ester group reduction in (XII) with LiBH4, followed by Swern oxidation of the resultant alcohol (XIII), furnished aldehyde (XIV). The aminoethyl phosphonium salt (XVI) was prepared by addition of N-ethyl cyclohexylamine (VI) to vinyl triphenylphosphonium bromide (XV). The corresponding ylide generated in situ from phosphonium salt (XV) and potassium bis(trimethylsilyl)amide was then subjected to a Wittig reaction with aldehyde (XIV) to afford the title (Z)-propenyl amine.

参考文献中间体

合成目标

【1】 Burgess, L.E.; The preparation of immunosuppressant SR-31747. Synth Commun 1997, 27, 12, 2181.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	59245	N-Ethylcyclohexanamine; N-Ethylcyclohexylamine; Vulkacit HX	5459-93-8	C₈H₁₇N	详情	详情
(VIII)	59247	4-Cyclohexylbenzoic acid	20029-52-1	C₁₃H₁₆O₂	详情	详情
(IX)	59248	4-Cyclohexylbenzoic acid methyl ester; Methyl 4-cyclohexylbenzoate	92863-34-8	C₁₄H₁₈O₂	详情	详情
(X)	59249	methyl 4-cyclohexyl-3-nitrobenzoate		C₁₄H₁₇NO₄	详情	详情
(XI)	59250	methyl 3-amino-4-cyclohexylbenzoate		C₁₄H₁₉NO₂	详情	详情
(XII)	59251	methyl 3-chloro-4-cyclohexylbenzoate		C₁₄H₁₇ClO₂	详情	详情
(XIII)	59252	(3-chloro-4-cyclohexylphenyl)methanol		C₁₃H₁₇ClO	详情	详情
(XIV)	59253	3-chloro-4-cyclohexylbenzaldehyde		C₁₃H₁₅ClO	详情	详情
(XV)	59254	triphenyl(vinyl)phosphonium bromide		C₂₀H₁₈BrP	详情	详情
(XVI)	59255	{2-[cyclohexyl(ethyl)amino]ethyl}(triphenyl)phosphonium bromide		C₂₈H₃₅BrNP	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

Alkylation of cyclohexyl ethylamine (VI) with propargyl bromide (VII) gives the tertiary amine (VIII). Then, palladium-catalyzed coupling between the propargylic amine (VIII) and aryl triflate (V) furnishes the disubstituted acetylene derivative (IX). Finally, semihydrogenation of the triple bond of (IX) in the presence of cyclohexene and Lindlar catalyst gives rise to the target cis-olefin.

参考文献中间体

合成目标

【1】 Paul, R.; Boigegrain, R.; Nisato, D.; Casellas, P.; Herbert, J.M.; Bourrie, B.; Bourrie, M.; Lair, P.; Vernieres, J.C. (Sanofi-Synthélabo); Benzene derivs., preparation method and pharmaceutical compsns. containing same. EP 1192122; FR 2794742; JP 2003502306; US 6482986; WO 0076953 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	62830	3,5-dichloro-4-tricyclo[3.3.1.1~3,7~]dec-2-ylphenyl trifluoromethanesulfonate		C₁₇H₁₇Cl₂F₃O₃S	详情	详情
(VI)	59245	N-Ethylcyclohexanamine; N-Ethylcyclohexylamine; Vulkacit HX	5459-93-8	C₈H₁₇N	详情	详情
(VII)	11176	3-Bromopropyne; 3-Bromo-1-propyne	106-96-7	C₃H₃Br	详情	详情
(VIII)	62831	N-ethyl-N-(2-propynyl)cyclohexanamine; N-cyclohexyl-N-ethyl-N-(2-propynyl)amine		C₁₁H₁₉N	详情	详情
(IX)	62832	N-[3-(3,5-dichloro-4-tricyclo[3.3.1.1~3,7~]dec-2-ylphenyl)-2-propynyl]-N-ethylcyclohexanamine; N-cyclohexyl-N-[3-(3,5-dichloro-4-tricyclo[3.3.1.1~3,7~]dec-2-ylphenyl)-2-propynyl]-N-ethylamine		C₂₇H₃₅Cl₂N	详情	详情

Extended Information