|
【结 构 式】 
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【分子编号】24786 【品名】1,6-dibromohexane 【CA登记号】629-03-8 |
【 分 子 式 】C6H12Br2 【 分 子 量 】243.96928 【元素组成】C 29.54% H 4.96% Br 65.5% |
合成路线1
该中间体在本合成路线中的序号：(II)Condensation of 2-chloro-4-methoxyphenol (I) with 1,6-dibromohexane (II) by means of K2CO3 in refluxing acetone to give 1-(2-chloro-4-methoxyphenoxy)-6-bromohexane (III), which is converted into the corresponding iodo derivative (IV) by treatment with NaI in refluxing acetone. Finally, (IV) is treated with the lithium salt of 3,5-heptanedione (V) in ether - DMF.
| 【1】 Collins, J.C.; Diana, G.D.; 3,4-Methylenedioxyphenoxy-alkyl diketones and keto-esters. DE 2435378 . |
| 【2】 Diana, G.D.; et al.; Antiviral acticity of some beta-diketones. 2. Aryloxy alkyl diketones. In vitro activity aganist both RNA and DNA viruses. J Med Chem 1977, 20, 6, 757-761. |
| 【3】 Hopkins, S.J.; Castaner, J.; Arildone. Drugs Fut 1978, 3, 1, 12. |
| 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) | 39686 | 2-chloro-4-methoxyphenol | 18113-03-6 | C7H7ClO2 | 详情 | 详情 |
| (II) | 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 |
| (III) | 39687 | 6-bromohexyl 2-chloro-4-methoxyphenyl ether; 1-[(6-bromohexyl)oxy]-2-chloro-4-methoxybenzene | C13H18BrClO2 | 详情 | 详情 | |
| (IV) | 39688 | 3-chloro-4-[(6-iodohexyl)oxy]phenyl methyl ether; 2-chloro-1-[(6-iodohexyl)oxy]-4-methoxybenzene | C13H18ClIO2 | 详情 | 详情 | |
| (V) | 39689 | 3,5-heptanedione | 7424-54-6 | C7H12O2 | 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 the lithium salt of 3,5-heptanedione (V) with 1,6-dibromohexane (II) in DMF giving 4-(6-bromohexyl)-3,5-heptanedione (VI), which is then condensed with 2-chloro-4-methoxyphenol (I) by means of NaH in DMF.
| 【1】 Diana, G.D.; et al.; Antiviral acticity of some beta-diketones. 2. Aryloxy alkyl diketones. In vitro activity aganist both RNA and DNA viruses. J Med Chem 1977, 20, 6, 757-761. |
| 【2】 Hopkins, S.J.; Castaner, J.; Arildone. Drugs Fut 1978, 3, 1, 12. |
合成路线3
该中间体在本合成路线中的序号：(I)1) Alkylation of diethyl malonate (II) with 1 6-dibromohexane (I) results in diethyl 6-bromohexylmaionate (III). Compound (II) is hydrolyzed to the monoester (IV), followed by condensation with paraformaldehyde in ethanol/piperidine/2-methylquinoline to yield ethyl 8-bromo-2-methyleneoctanoate (V), which is oxidized with permaleic acid to (VI). Subsequent reaction with 4-chlorophenolate produces etomoxir.
| 【1】 Eistetter, K.; Ludwig, G.; Rapp, E.; Wolf, H. (Byk Gulden Lomberg Chemische Fabrik GmbH); Phenoxyalkoxyalkyl- and phenoxyalkyl-substd. oxiranecarboxylic acids, their use and medicaments containing them. EP 0046590; US 4337267 . |
| 【2】 Eistetter, K.; Wolf, H.P.O.; ETOMOXIR. Drugs Fut 1986, 11, 12, 1034. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 62997 | 4-chlorobenzenolate | C6H4ClO | 详情 | 详情 | ||
| (I) | 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 |
| (II) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
| (III) | 24864 | diethyl 2-(6-bromohexyl)malonate | C13H23BrO4 | 详情 | 详情 | |
| (IV) | 24865 | 8-bromo-2-(ethoxycarbonyl)octanoic acid | C11H19BrO4 | 详情 | 详情 | |
| (V) | 24866 | ethyl 2-(6-bromohexyl)acrylate | C11H19BrO2 | 详情 | 详情 | |
| (VI) | 24867 | ethyl 2-(6-bromohexyl)-2-oxiranecarboxylate | C11H19BrO3 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)2) Alternatively, etomoxir can be prepared as follows: Alkylation of 4-chlorophenol with 1,6-dibromohexane (I) yields 1 bromo-6-(4-chlorophenoxy)hexane (VII). Diethyl malonate (II) is alkylated by (VII), yielding (VIII), followed by hydrolysis to the monoester (IX), which is condensed with para formaldehyde/pyridine/piperidine to give ethyl 8-(4-chlorophenoxy)-2-methyleneoctanoate (IX). Oxidation with m-chloroperbenzoic acid produces etomoxir.
| 【1】 Eistetter, K.; Ludwig, G.; Rapp, E.; Wolf, H. (Byk Gulden Lomberg Chemische Fabrik GmbH); Phenoxyalkoxyalkyl- and phenoxyalkyl-substd. oxiranecarboxylic acids, their use and medicaments containing them. EP 0046590; US 4337267 . |
| 【2】 Eistetter, K.; Wolf, H.P.O.; ETOMOXIR. Drugs Fut 1986, 11, 12, 1034. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 35543 | 4-chlorophenol | 106-48-9 | C6H5ClO | 详情 | 详情 | |
| (I) | 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 |
| (II) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
| (VII) | 24870 | 6-bromohexyl 4-chlorophenyl ether | C12H16BrClO | 详情 | 详情 | |
| (VIII) | 24871 | diethyl 2-[6-(4-chlorophenoxy)hexyl]malonate | C19H27ClO5 | 详情 | 详情 | |
| (IX) | 24872 | 8-(4-chlorophenoxy)-2-(ethoxycarbonyl)octanoic acid | C17H23ClO5 | 详情 | 详情 | |
| (X) | 24873 | ethyl 2-[6-(4-chlorophenoxy)hexyl]acrylate | C17H23ClO3 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)The reaction of 4-phenyl-1-butanol (I) with 1,6-dibromohexane by means of NaH in THF gives the ether derivative (III), which is then condensed with 5-(2-amino-1-hydroxyethyl)-2-hydroxybenzyl alcohol (IV) by means of KI and triethylamine in hot DMF.
| 【1】 Skidmore, I.F.; Lunts, L.H.C.; Finch, H.; Naylor, A. (Glaxo Group Ltd.); Phenethanolamine derivs. BE 0899448; DE 3414752; ES 8609209; FR 2545482; GB 2140800; GB 2176476; JP 1988264443; JP 1994087800; US 4992474; US 5091422 . |
| 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) | 27291 | 4-phenyl-1-butanol | 3360-41-6 | C10H14O | 详情 | 详情 |
| (II) | 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 |
| (III) | 31479 | 1-[4-[(6-bromohexyl)oxy]butyl]benzene; 6-bromohexyl-4-phenylbutyl ether; 6-Bromohexyloxybutylbenzene | 94749-73-2 | C16H25BrO | 详情 | 详情 |
| (IV) | 31480 | 4-(2-amino-1-hydroxyethyl)-2-(hydroxymethyl)phenol | C9H13NO3 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(II)The reaction of 4-phenyl-1-butanol (I) with 1,6-dibromohexane (II) by means of KOH and tetrabutylammonium bisulfate gives the butyl hexyl ether (III), which is condensed with 2-aminoacetaldehyde dimethylacetal (IV) in refluxing toluene yielding 2-[6-(4-phenylbutoxy)hexylamino]acetaldehyde dimethylacetal (V). The protection of the amino group of (V) with N-(benzyloxycarbonyloxy)succinimide and triethylamine in acetone affords the carbamate (VI), which is treated with TsOH in acetone to provide the acetaldehyde derivative (VII). The condensation of (VII) with 6-bromo-2,2-dimethyl-1,3-benzodioxan (VIII) (obtained by cyclization of phenol (IX) with acetone and AlCl3) by means of Mg in THF gives the expected carbinol (X), which is deprotected with H2 over Pd/C in methanol yielding the aminoethanol derivative (XI). Finally, this compound is treated with HCl in methanol/water to open the 1,3-dioxane ring and afford the target compound.
| 【1】 Marquillas Olondriz, F.; Dalmases Barjoan, P.; Bessa Bellmunt, J. (Laboratorios Vita, SA); New derivs. of 6-(4-phenylbutoxy)hexylamine and process for producing salmeterol. ES 2142771; WO 0018722 . |
| 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) | 27291 | 4-phenyl-1-butanol | 3360-41-6 | C10H14O | 详情 | 详情 |
| (II) | 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 |
| (III) | 31479 | 1-[4-[(6-bromohexyl)oxy]butyl]benzene; 6-bromohexyl-4-phenylbutyl ether; 6-Bromohexyloxybutylbenzene | 94749-73-2 | C16H25BrO | 详情 | 详情 |
| (IV) | 34158 | aminoacetaldehyde dimethylacetal; 2,2-dimethoxy-1-ethanamine; 2,2-dimethoxyethylamine | 22483-09-6 | C4H11NO2 | 详情 | 详情 |
| (V) | 36932 | N-(2,2-dimethoxyethyl)-N-[6-(4-phenylbutoxy)hexyl]amine; N-(2,2-dimethoxyethyl)-6-(4-phenylbutoxy)-1-hexanamine | C20H35NO3 | 详情 | 详情 | |
| (VI) | 36933 | benzyl 2,2-dimethoxyethyl[6-(4-phenylbutoxy)hexyl]carbamate | C28H41NO5 | 详情 | 详情 | |
| (VII) | 36934 | benzyl 2-oxoethyl[6-(4-phenylbutoxy)hexyl]carbamate | C26H35NO4 | 详情 | 详情 | |
| (VIII) | 36935 | 4-bromo-2-(hydroxymethyl)phenol | 2316-64-5 | C7H7BrO2 | 详情 | 详情 |
| (IX) | 36936 | 6-bromo-2,2-dimethyl-4H-1,3-benzodioxine | C10H11BrO2 | 详情 | 详情 | |
| (X) | 36937 | benzyl 2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethyl[6-(4-phenylbutoxy)hexyl]carbamate | C36H47NO6 | 详情 | 详情 | |
| (XI) | 36938 | 1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-[[6-(4-phenylbutoxy)hexyl]amino]-1-ethanol | C28H41NO4 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(I)The condensation of 1,6-dibromohexane (I) with 4-phenyl-1-butanol (II) by means of NaOH under phase transfer catalysis gives 6-(4-phenylbutoxy)hexyl bromide (III), which is condensed with benzylamine (IV) by means of Cs2CO3 in hot DMF to yield the secondary amine (V). The condensation of (V) with methyl alpha-bromo 4-acetylsalicylate (VI) by means of DIEA in refluxing THF affords the tertiary amine (VII), which is submitted to a reductive deuteration by means of deuterated LiAlD4 in THF to provide the trideuterated intermediate (VIII). Finally this compound is deprotected by hydrogenation with H2 over Pd/C in methanol to give rise to the target trideuterated salmeterol.
| 【1】 Molinski, T.F.; Stanley, S.D.; Improved synthesis of 13C,2H3- and 2H3-salmeterol by Cs2CO3-mediated monoalkylation of a primary amine. J Label Compd Radiopharm 2002, 45, 9, 755. |
| 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) | 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 |
| (II) | 27291 | 4-phenyl-1-butanol | 3360-41-6 | C10H14O | 详情 | 详情 |
| (III) | 31479 | 1-[4-[(6-bromohexyl)oxy]butyl]benzene; 6-bromohexyl-4-phenylbutyl ether; 6-Bromohexyloxybutylbenzene | 94749-73-2 | C16H25BrO | 详情 | 详情 |
| (IV) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (V) | 35836 | methyl 5-(2-bromoacetyl)-2-hydroxybenzoate | C10H9BrO4 | 详情 | 详情 | |
| (VI) | 35837 | N-benzyl-6-(4-phenylbutoxy)-1-hexanamine; N-benzyl-N-[6-(4-phenylbutoxy)hexyl]amine | C23H33NO | 详情 | 详情 | |
| (VII) | 35838 | methyl 5-(2-[benzyl[6-(4-phenylbutoxy)hexyl]amino]acetyl)-2-hydroxybenzoate | C33H41NO5 | 详情 | 详情 | |
| (VIII) | 35839 | 4-(2-[benzyl[6-(4-phenylbutoxy)hexyl]amino]-1-hydroxyethyl)-2-(hydroxymethyl)phenol | C32H43NO4 | 详情 | 详情 | |
| (VIII) | 57250 | 4-(2-{benzyl[6-(4-phenylbutoxy)hexyl]amino}-1-hydroxyethyl)-2-(hydroxymethyl)phenol | C32H43NO4 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(II)The condensation of 4-phenyl-1-butanol (I) with 1,6-dibromohexane (II) by means of NaH in THF gives the ether (III), which is condensed with benzylamine (IV) by means of NaI and TEA in DMSO to yield the secondary amine (V). The condensation of (V) with 5-(bromoacetyl)-2-hydroxybenzaldehyde (VI) in refluxing acetonitrile affords the tertiary amine (VII). The reduction of both carbonyl groups of (VII) by means of NaBH4 in methanol affords the dihydroxy amine (VIII), which is finally debenzylated by means of h2 over Pd/C in the same solvent to provide the target salmeterol. The intermediate 5-(bromoacetyl)-2-hydroxybenzaldehyde (VI) has been obtained by Friedel Crafts condensation of 2-hydroxybenzaldehyde (IX) with bromoacetyl chloride (X) by means of AlCl3 in dichloromethane.
| 【1】 Rong, Y.; Ruoho, A.E.; A new synthetic approach to salmeterol. Synth Commun 1999, 29, 12, 2155. |
| 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) | 27291 | 4-phenyl-1-butanol | 3360-41-6 | C10H14O | 详情 | 详情 |
| (II) | 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 |
| (III) | 31479 | 1-[4-[(6-bromohexyl)oxy]butyl]benzene; 6-bromohexyl-4-phenylbutyl ether; 6-Bromohexyloxybutylbenzene | 94749-73-2 | C16H25BrO | 详情 | 详情 |
| (IV) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (V) | 35837 | N-benzyl-6-(4-phenylbutoxy)-1-hexanamine; N-benzyl-N-[6-(4-phenylbutoxy)hexyl]amine | C23H33NO | 详情 | 详情 | |
| (VI) | 50873 | 5-(2-bromoacetyl)-2-hydroxybenzaldehyde | C9H7BrO3 | 详情 | 详情 | |
| (VII) | 50874 | 5-(2-[benzyl[6-(4-phenylbutoxy)hexyl]amino]acetyl)-2-hydroxybenzaldehyde | C32H39NO4 | 详情 | 详情 | |
| (VIII) | 35839 | 4-(2-[benzyl[6-(4-phenylbutoxy)hexyl]amino]-1-hydroxyethyl)-2-(hydroxymethyl)phenol | C32H43NO4 | 详情 | 详情 | |
| (IX) | 21351 | 2-Hydroxybenzaldehyde;Salicylic aldehyde；2-Formylphenol;salicylaldehyde | 90-02-8 | C7H6O2 | 详情 | 详情 |
| (X) | 27903 | 2-Bromoacetyl chloride | 22118-09-8 | C2H2BrClO | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(X)The reaction of benzohydroxamic acid (I) with benzyl bromide (II) by means of NaOH on ethanol gives the corresponding benzyl ester (III), which is treated with HCl yielding O-benzylhydroxylamine (IV). The reaction of (IV) with dicyaniamide (V) in ethanol affords the biguanide (VI), which is cyclized with cyclopentanone (VII) and HCl giving 1-benzyloxy-2,2-dimethyl-1,2-dihydro-1,3,5-triazine-4,6-diamine (VIII). The debenzylation of (VIII) with H2 over PtO2 in ethanol yields 1-hydroxy-2,2-dimethyl-1,2-dihydro-1,3,5-triazine-4,6-diamine (IX), which is finally condensed with 1,6-dibromohexane (X) by means of NaOH in methanol.
| 【1】 Zhang, X.P.; Shen, J.; Xin, Z.M.; Qiu, Q.P.; Zhou, W.C.; Synthesis and antiprotozoal activities of some new triazine derivatives including a new antitrypanosomal agent: SIPI-1029. Acta Pharm Sin 1996, 31, 11, 823. |
| 【2】 Zhou, W.; Zhang, X.; Trybizine Hydrochloride. Drugs Fut 1999, 24, 10, 1084. |
| 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) | 24777 | N-hydroxybenzamide | 495-18-1 | C7H7NO2 | 详情 | 详情 |
| (II) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
| (III) | 24779 | N-(benzyloxy)benzamide | C14H13NO2 | 详情 | 详情 | |
| (IV) | 14640 | O-benzylhydroxylamine; 1-[(aminooxy)methyl]benzene | 622-33-3 | C7H9NO | 详情 | 详情 |
| (V) | 23611 | N-cyanoguanidine | 461-58-5 | C2H4N4 | 详情 | 详情 |
| (VI) | 24782 | 1-[([[[[amino(imino)methyl]amino](imino)methyl]amino]oxy)methyl]benzene | C9H13N5O | 详情 | 详情 | |
| (VII) | 15113 | cyclopentanone | 120-92-3 | C5H8O | 详情 | 详情 |
| (VIII) | 24784 | 10-(benzyloxy)-6,8,10-triazaspiro[4.5]deca-6,8-diene-7,9-diamine | C14H19N5O | 详情 | 详情 | |
| (IX) | 24785 | 7,9-diamino-6,8,10-triazaspiro[4.5]deca-7,9-dien-6-ol | C7H13N5O | 详情 | 详情 | |
| (X) | 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(X)The reaction of benzohydroxamic acid (I) with 1,6-dibromohexane (X) by means of NaOH in methanol gives the bis benzohydroxamic ester (XI), which is treated with HCl to afford the subituted bis hydroxylamine (XII). The reaction of (XII) with dicyandiamide (V) in ethanol yields the bis biguanide (XIII), which is finally cyclized with cyclopentanone (VII) and HCl as before.
| 【1】 Zhang, X.P.; Shen, J.; Xin, Z.M.; Qiu, Q.P.; Zhou, W.C.; Synthesis and antiprotozoal activities of some new triazine derivatives including a new antitrypanosomal agent: SIPI-1029. Acta Pharm Sin 1996, 31, 11, 823. |
| 【2】 Zhou, W.; Zhang, X.; Trybizine Hydrochloride. Drugs Fut 1999, 24, 10, 1084. |
| 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) | 24777 | N-hydroxybenzamide | 495-18-1 | C7H7NO2 | 详情 | 详情 |
| (V) | 23611 | N-cyanoguanidine | 461-58-5 | C2H4N4 | 详情 | 详情 |
| (VII) | 15113 | cyclopentanone | 120-92-3 | C5H8O | 详情 | 详情 |
| (X) | 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 |
| (XI) | 24787 | N-([6-[(benzoylamino)oxy]hexyl]oxy)benzamide | C20H24N2O4 | 详情 | 详情 | |
| (XII) | 24788 | 1,6-bis(aminooxy)hexane | C6H16N2O2 | 详情 | 详情 | |
| (XIII) | 24789 | 1,6-bis([[[[amino(imino)methyl]amino](imino)methyl]amino]oxy)hexane | C10H24N10O2 | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：Lithiation of 1-(N-N-dimethylsulfamoyl)imidazole (I) followed by reaction with tert-butyldimethylsilyl chloride produced the 2-silyl protected imidazole (II). Further lithiation of (II) allowed the introduction of a bromohexyl group at position 5 upon treatment with 1,6-dibromohexane yielding (III). Bromide (III) was subsequently converted into primary amine (VI) through a Gabriel synthesis involving condensation with potassium phthalimide (IV) with concomitant desilylation, and then hydrazinolysis of the resulting alkylated phthalimide (V). Condensation of amine (VI) with naphthalene-2-sulfonyl chloride (VII) furnished sulfonamide (VIII). The sulfamoyl protecting group of (VIII) was finally removed by hydrolysis with HCl.
| 【1】 Tozer, M.J.; Kalindjian, B.; Pether, M.J.; Watt, G.F.; Shankley, N.P.; Harper, E.A.; From histamine to imidazolylalkyl-sulfonamides: The design of a novel series of histamine H3-receptor antagonists. Bioorg Med Chem Lett 1999, 9, 13, 1825. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 | |
| (I) | 11036 | N,N-Dimethyl-1H-imidazole-1-sulfonamide | 78162-58-0 | C5H9N3O2S | 详情 | 详情 |
| (II) | 11037 | 2-[tert-Butyl(dimethyl)silyl]-N,N-dimethyl-1H-imidazole-1-sulfonamide | C11H23N3O2SSi | 详情 | 详情 | |
| (III) | 27986 | 5-(6-bromohexyl)-2-[tert-butyl(dimethyl)silyl]-N,N-dimethyl-1H-imidazole-1-sulfonamide | C17H34BrN3O2SSi | 详情 | 详情 | |
| (IV) | 10926 | (1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)potassium | C8H4KNO2 | 详情 | 详情 | |
| (V) | 27987 | 5-[6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)hexyl]-N,N-dimethyl-1H-imidazole-1-sulfonamide | C19H24N4O4S | 详情 | 详情 | |
| (VI) | 27988 | 5-(6-aminohexyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide | C11H22N4O2S | 详情 | 详情 | |
| (VII) | 27989 | 2-naphthalenesulfonyl chloride | 93-11-8 | C10H7ClO2S | 详情 | 详情 |
| (VIII) | 27990 | N,N-dimethyl-5-[6-[(2-naphthylsulfonyl)amino]hexyl]-1H-imidazole-1-sulfonamide | C21H28N4O4S2 | 详情 | 详情 |
合成路线12
该中间体在本合成路线中的序号：(IX)Acetylation of o-aminophenol (I) gives o-hydroxy acetanilide (II), which is then protected as the benzyl ether (III) with benzyl bromide and K2CO3. Treatment of acetamide (III) with P2S5 affords the corresponding thioamide (IV), and subsequent S-methylation of (IV) gives rise to the thioimidate (V). Cyclization of thioimidate (V) with 4-biphenylcarboxylic acid hydrazide (VI) in hot DMF leads to the triazole derivative (VII). After benzyl group hydrogenolysis in (VII), the resultant phenol (VIII) is alkylated with 1,6-dibromohexane (IX) to produce the bromohexyl ether (X). Finally, condensation of bromide (X) with N-methylpiperazine (XI) furnishes the title compound.
| 【1】 Kakefuda, A.; et al.; Synthesis and pharmacological evaluation of 5-(4-biphenyl)-3-methyl-4-phenyl-1,2,4-triazole derivatives as a novel class of selective antagonists for the human vasopressin V1A receptor. J Med Chem 2002, 45, 12, 2589. |
| 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) | 18663 | o-aminophenol; 2-aminophenol | 95-55-6 | C6H7NO | 详情 | 详情 |
| (II) | 56976 | 2-Acetamidophenol; 2-Hydroxyacetanilide; o-Acetamidophenol; o-Hydroxyacetanilide | 614-80-2 | C8H9NO2 | 详情 | 详情 |
| (III) | 56977 | N-[2-(benzyloxy)phenyl]acetamide | C15H15NO2 | 详情 | 详情 | |
| (IV) | 56978 | N-[2-(benzyloxy)phenyl]ethanethioamide | C15H15NOS | 详情 | 详情 | |
| (V) | 56979 | methyl N-[2-(benzyloxy)phenyl]ethanimidothioate | C16H17NOS | 详情 | 详情 | |
| (VI) | 56980 | 4-Biphenylcarboxylic acid hydrazide; 4-Phenylbenzhydrazide | 18622-23-6 | C13H12N2O | 详情 | 详情 |
| (VII) | 56981 | benzyl 2-(3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazol-4-yl)phenyl ether; 4-[2-(benzyloxy)phenyl]-3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazole | C28H23N3O | 详情 | 详情 | |
| (VIII) | 56982 | 2-(3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazol-4-yl)phenol | C21H17N3O | 详情 | 详情 | |
| (IX) | 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 |
| (X) | 56983 | 3-[1,1'-biphenyl]-4-yl-4-{2-[(6-bromohexyl)oxy]phenyl}-5-methyl-4H-1,2,4-triazole; 2-(3-[1,1'-biphenyl]-4-yl-5-methyl-4H-1,2,4-triazol-4-yl)phenyl 6-bromohexyl ether | C27H28BrN3O | 详情 | 详情 | |
| (XI) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |