SR-31747, CM-31747, -Drug Synthesis Database

【结构式】

【药物名称】SR-31747, CM-31747

【化学名称】3-(3-Chloro-4-cyclohexylphenyl)-N-cyclohexyl-N-ethyl-2(Z)-propenylamine hydrochloride

【CA登记号】132173-07-0

【分子式】C₂₃H₃₅Cl₂N

【分子量】396.4481

【开发单位】Sanofi-synthélabo (Originator)

【药理作用】Antiarthritic Drugs, Breast Cancer Therapy, IMMUNOMODULATING AGENTS, Immunosuppressants, Oncolytic Drugs, Prostate Cancer Therapy, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, sigma Receptor Antagonists

合成路线1 合成路线2

合成路线1

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

【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

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

【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

Extended Information