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【结 构 式】 
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【分子编号】15540 【品名】4-methylphenylboronic acid; p-Tolylboronic acid 【CA登记号】5720-05-8 |
【 分 子 式 】C7H9BO2 【 分 子 量 】135.95826 【元素组成】C 61.84% H 6.67% B 7.95% O 23.54% |
合成路线1
该中间体在本合成路线中的序号：(VI)1) The cyclization of aniline (I) with propionylacetic acid methyl ester (II) by means of p-toluenesulfonic acid in refluxing cyclohexane gives 2-ethylquinolin-4(1H)-one (III), which is condensed with 5-[4'-(bromomethyl)biphenyl-2-yl]-2-(triphenylmethyl)tetrazole (IV) by means of NaH in DMF, yielding 2-ethyl-4-[2'-[1-(triphenylmethyl)tetrazol-5-yl]biphenyl-4-ylmethoxy] quinoline (V). Finally, this compound is deprotected with HCl in ethanol - methanol. 2) The condensation of 4-methylphenylboronic acid (VI) with 2-bromobenzonitrile (VII) by means of Na2CO3 and PdCl2 in toluene - methanol gives 2-(4-methylphenyl)benzonitrile (VIII), which is brominated with N-bromosuccinimide (NBS) and azobis(isobutyronitrile) (AIBN) in hot chlorobenzene, yielding the bromomethyl derivative (IX). The condensation of (IX) with quinolone (III) by means of K2CO3 in N-methylpyrrolidone affords 4-(2'-cyanobiphenyl-4-ylmethoxy)-2-ethylquinoline (X), which is treated with tributyltin hydrazide in refluxing toluene to afford 2-ethyl-4-[2'-[2-(tributyltin)tetrazol-5-yl]biphenyl-4-ylmethoxy] quinoline (XI). Finally, this compound is deprotected with NaNO2 and HCl in cool water.
| 【1】 Roberts, D.A.; Russell, S.T.; Pearce, R.J. (AstraZeneca plc); Quinoline derivs., process for their preparation and their use as medicaments. AU 9160955; EP 0412848; GB 2234748; JP 1991169863; US 5444071 . |
| 【2】 Prous, J.; Castaner, J.; Graul, A.; ICI-D8731. Drugs Fut 1993, 18, 5, 428. |
| 【3】 Bradbury, R.H.; Allott, C.P.; Dennis, M.; et al.; New nonpeptide angiotensin II receptor antagonists. 2. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)quinoline derivatives. J Med Chem 1992, 35, 22, 4027. |
| 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) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (II) | 15536 | methyl 3-oxopentanoate | 30414-53-0 | C6H10O3 | 详情 | 详情 |
| (III) | 15537 | 2-ethyl-4(1H)-quinolinone | C11H11NO | 详情 | 详情 | |
| (IV) | 15538 | 5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-2-trityl-2H-1,2,3,4-tetraazole | 124750-51-2 | C33H25BrN4 | 详情 | 详情 |
| (V) | 15539 | 2-ethyl-4-quinolinyl [2'-(2-trityl-2H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl ether; 2-ethyl-4-[[2'-(2-trityl-2H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methoxy]quinoline | C44H35N5O | 详情 | 详情 | |
| (VI) | 15540 | 4-methylphenylboronic acid; p-Tolylboronic acid | 5720-05-8 | C7H9BO2 | 详情 | 详情 |
| (VII) | 15541 | o-bromobenzonitrile; 2-bromobenzonitrile | 2042-37-7 | C7H4BrN | 详情 | 详情 |
| (VIII) | 13929 | 2-Cyano-4'-methylbiphenyl; 4'-Methyl[1,1'-biphenyl]-2-carbonitrile | 114772-53-1 | C14H11N | 详情 | 详情 |
| (IX) | 15332 | 4'-(bromomethyl)[1,1'-biphenyl]-2-carbonitrile; 4'-bromomethyl-2-cyanobiphenyl | 114772-54-2 | C14H10BrN | 详情 | 详情 |
| (X) | 15544 | 4'-[[(2-ethyl-4-quinolinyl)oxy]methyl][1,1'-biphenyl]-2-carbonitrile | C25H20N2O | 详情 | 详情 | |
| (XI) | 15545 | 5-[4'-(2-Ethylquinolin-4-yloxymethyl)biphenyl-2-yl]-2-(tributylstannyl)-2H-tetrazole | C37H47N5OSn | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)3) The condensation of 2-bromobenzoic acid (XII) with 4-nitroaniline (XIII) by means of SOCl2 in DMF gives the corresponding amide (XIV), which is cyclized with sodium azide and SOCl2 in acetonitrile - DMF, yielding 5-(2-bromophenyl)-1-(4-nitrophenyl)tetrazole (XV). The condensation of (XV) with the boronic acid (VI, Scheme 1) by means of Na2CO3 and tetrakis(triphenylphosphine)palladium in methanol - water - toluene affords 5-(4'-methylbiphenyl-2-yl)-1-(4-nitrophenyl)tetrazole (XVI), which is brominated with NBS and AIBN to the corresponding bromomethyl derivative (XVII). The condensation of (XVII) with quinolone (III, Scheme 1) by means of K2CO3 in hot N-methylpyrrolidone gives 2-ethyl-4-[2'-[1-(4-nitrophenyl)tetrazol-5-yl]biphenyl-4-ylmethoxy] quinoline (XVIII), which is finally deprotected with NaH and propanethiol in N-methylpyrrolidone. 4) The dehydration of the boronic acid (VI), followed by bromination with bromine and AIBN, gives 4-(bromomethyl)boronic anhydride (XIX), which is condensed with quinolone (III) by means of K2CO3 in N-methylpyrrolidone, yielding 4-(2-ethylquinolin-4-yloxymethyl)phenylboronic acid (XX). The condensation of (XX) with the bromophenyl-tetrazole (XV) by means of K2CO3 and tetrakis(triphenylphosphine)palladium in water - methanol - toluene yields compound (XVIII), already obtained (5). Scheme 2. 5) The reaction of the boronic acid (VI) with 2,2-dimethylpropane-1,3-diol (XXI) in refluxing cyclohexane gives the cyclic boronic ester (XXII), which is brominated with BBS as before to the bromomethyl derivative (XXIII). The condensation of (XXIII) with quinolone (III) affords 2-[4-(2-ethylquinolin-4-yloxymethyl)phenyl]-5,5-dimethyl-1,3,2-dioxaborinane (XXIV), which is condensed with (XV) as before to give (XVIII), already obtained.
| 【1】 Roberts, D.A.; Russell, S.T.; Pearce, R.J. (AstraZeneca plc); Quinoline derivs., process for their preparation and their use as medicaments. AU 9160955; EP 0412848; GB 2234748; JP 1991169863; US 5444071 . |
| 【2】 Prous, J.; Castaner, J.; Graul, A.; ICI-D8731. Drugs Fut 1993, 18, 5, 428. |
| 【3】 Bradbury, R.H.; Allott, C.P.; Dennis, M.; et al.; New nonpeptide angiotensin II receptor antagonists. 2. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)quinoline derivatives. J Med Chem 1992, 35, 22, 4027. |
| 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) | 15540 | 4-methylphenylboronic acid; p-Tolylboronic acid | 5720-05-8 | C7H9BO2 | 详情 | 详情 |
| (XII) | 15546 | 2-bromobenzoic acid; o-bromobenzoic acid | 88-65-3 | C7H5BrO2 | 详情 | 详情 |
| (XIII) | 15547 | 4-nitrophenylamine; p-Nitroaniline; 4-nitroaniline | 100-01-6 | C6H6N2O2 | 详情 | 详情 |
| (XIV) | 15548 | 2-bromo-N-(4-nitrophenyl)benzamide | C13H9BrN2O3 | 详情 | 详情 | |
| (XV) | 11451 | 5-(2-Bromophenyl)-1-(4-nitrophenyl)-1H-1,2,3,4-tetraazole | C13H8BrN5O2 | 详情 | 详情 | |
| (XVI) | 15550 | 5-(4'-methyl[1,1'-biphenyl]-2-yl)-1-(4-nitrophenyl)-1H-1,2,3,4-tetraazole | C20H15N5O2 | 详情 | 详情 | |
| (XVII) | 15551 | 5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-1-(4-nitrophenyl)-1H-1,2,3,4-tetraazole | C20H14BrN5O2 | 详情 | 详情 | |
| (XVIII) | 15552 | 2-ethyl-4-quinolinyl [2'-[1-(4-nitrophenyl)-1H-1,2,3,4-tetraazol-5-yl][1,1'-biphenyl]-4-yl]methyl ether; 2-ethyl-4-([2'-[1-(4-nitrophenyl)-1H-1,2,3,4-tetraazol-5-yl][1,1'-biphenyl]-4-yl]methoxy)quinoline | C20H14BrN5O2 | 详情 | 详情 | |
| (XIX) | 15553 | 1,3-bis[4-(bromomethyl)phenyl]-3-hydroxy-1-diboroxanol | C14H14B2Br2O3 | 详情 | 详情 | |
| (XX) | 15554 | 4-[[(2-ethyl-4-quinolinyl)oxy]methyl]phenylboronic acid | C18H18BNO3 | 详情 | 详情 | |
| (XXI) | 12641 | Neopentyl glycol; 2,2-Dimethyl-1,3-propanediol | 126-30-7 | C5H12O2 | 详情 | 详情 |
| (XXII) | 15556 | 5,5-dimethyl-2-(4-methylphenyl)-1,3,2-dioxaborinane | C12H17BO2 | 详情 | 详情 | |
| (XXIII) | 15557 | 2-[4-(bromomethyl)phenyl]-5,5-dimethyl-1,3,2-dioxaborinane | C12H16BBrO2 | 详情 | 详情 | |
| (XXIV) | 15558 | 4-[[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzyl]oxy]-2-ethylquinoline; 4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzyl 2-ethyl-4-quinolinyl ether | C23H26BNO3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)4-Bromobenzenesulfonyl chloride (I) was condensed with aminoisoxazole (II) in pyridine to afford sulfonamide (III). Subsequent Suzuki coupling of (III) to 4-tolylboronic acid (IV) under palladium catalysis provided biphenylsulfonamide (V), which was finally brominated with N-bromosuccinimide in cold CH2Cl2 to furnish the target bromoisoxazole.
| 【1】 Chan, M.F.; Kois, A.; Verner, E.J.; Raju, B.G.; Castillo, R.S.; Wu, C.; Okun, I.; Stavros, F.D.; Balaji, V.N.; The discovery and structure-activity relationships of nonpeptide, low molecular weight antagonists selective for the endothelin ETB receptor. Bioorg Med Chem 1998, 6, 12, 2301. |
| 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) | 18964 | 4-bromobenzenesulfonyl chloride | 98-58-8 | C6H4BrClO2S | 详情 | 详情 |
| (II) | 17834 | 3-methyl-5-isoxazolylamine; 3-methyl-5-isoxazolamine; 5-Amino-3-methylisoxazole | 14678-02-5 | C4H6N2O | 详情 | 详情 |
| (III) | 22375 | 4-bromo-N-(3-methyl-5-isoxazolyl)benzenesulfonamide | C10H9BrN2O3S | 详情 | 详情 | |
| (IV) | 15540 | 4-methylphenylboronic acid; p-Tolylboronic acid | 5720-05-8 | C7H9BO2 | 详情 | 详情 |
| (V) | 22377 | 4'-methyl-N-(3-methyl-5-isoxazolyl)[1,1'-biphenyl]-4-sulfonamide | C17H16N2O3S | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)Suzuki coupling of 4-tolylboronic acid (I) with 2-bromothiophene (II) under palladium catalysis provided tolylthiophene (III). Subsequent chlorosulfonation of (III) with chlorosulfonic acid in the presence of PCl5 and POCl3 afforded sulfonyl chloride (IV), which was finally condensed with the aminoisoxazole (V) using NaH in THF to furnish the target sulfonamide.
| 【1】 Chan, M.F.; Kois, A.; Verner, E.J.; Raju, B.G.; Castillo, R.S.; Wu, C.; Okun, I.; Stavros, F.D.; Balaji, V.N.; The discovery and structure-activity relationships of nonpeptide, low molecular weight antagonists selective for the endothelin ETB receptor. Bioorg Med Chem 1998, 6, 12, 2301. |
| 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) | 15540 | 4-methylphenylboronic acid; p-Tolylboronic acid | 5720-05-8 | C7H9BO2 | 详情 | 详情 |
| (II) | 13681 | 2-Bromothiophene | 1003-09-4 | C4H3BrS | 详情 | 详情 |
| (III) | 22380 | 2-(4-methylphenyl)thiophene | C11H10S | 详情 | 详情 | |
| (IV) | 22381 | 5-(4-methylphenyl)-2-thiophenesulfonyl chloride | C11H9ClO2S2 | 详情 | 详情 | |
| (V) | 22382 | 4-bromo-3-methyl-5-isoxazolamine; 4-bromo-3-methyl-5-isoxazolylamine | C4H5BrN2O | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(III)The reaction of tropanone (I) with N,N-bis(trifluoromethylsulfonyl)aniline and sodium hexamethyldisilylazide in THF gives the enol triflate (II), which is condensed with 4-methylphenylboronic acid (III) by means of palladium tetrakis(triphenylphosphine) yielding the p-tolyltropane (IV). The hydrolysis of the methyl ester of (IV) with KOH affords the carboxylic acid (V), which is treated with diphenoxyphosphoryl azide in hot toluene to give the isocyanate (VI). The hydrolysis of (VI) in refluxing ethanol yields the tropanone (VII), which by reaction with phenylmagnesium bromide in ethyl ether affords the diphenyltropanol (VIII). The dehydration of (VIII) with refluxing conc. HBr gives the diphenyltropene (XI), which by reaction with phenyl chloroformate in dichloromethane yields the N-carboxylate (XII). The reduction of (XII) with H2 over Pd/C in methanol affords a mixture of the (exo, exo) (XIII) and (endo, endo) (XIV) compounds, which is reduced with LiAlH4 in ethyl ether providing a mixture of the target compound and its (endo, endo) isomer (XV) that is separated by chromatography.
| 【1】 Jiang, S.; Chang, A.-C.; Abraham, P.; Kuhar, M.J.; Carroll, F.I.; Synthesis and transporter binding properties of (R)-2beta,3beta- and (R)-2alpha,3alpha-diaryltropanes. Bioorg Med Chem Lett 1998, 8, 24, 3689. |
| 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) | 27655 | methyl (1R,5S)-8-methyl-3-oxo-8-azabicyclo[3.2.1]octane-2-carboxylate | C10H15NO3 | 详情 | 详情 | |
| (II) | 27656 | methyl (1R,5S)-8-methyl-3-[[(trifluoromethyl)sulfonyl]oxy]-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate | C11H14F3NO5S | 详情 | 详情 | |
| (III) | 15540 | 4-methylphenylboronic acid; p-Tolylboronic acid | 5720-05-8 | C7H9BO2 | 详情 | 详情 |
| (IV) | 27657 | methyl (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate | C17H21NO2 | 详情 | 详情 | |
| (V) | 27658 | (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylic acid | C16H19NO2 | 详情 | 详情 | |
| (VI) | 27659 | (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-en-2-yl isocyanate | C16H18N2O | 详情 | 详情 | |
| (VII) | 27660 | (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octan-2-one | C15H19NO | 详情 | 详情 | |
| (VIII) | 27661 | (1R,5S)-8-methyl-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octan-2-ol | C21H25NO | 详情 | 详情 | |
| (XI) | 27662 | (1R,5S)-8-methyl-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]oct-2-ene | C21H23N | 详情 | 详情 | |
| (XII) | 27663 | phenyl (1R,5S)-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate | C27H25NO2 | 详情 | 详情 | |
| (XIII) | 27664 | phenyl (1R,2R,3S,5S)-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate | C27H27NO2 | 详情 | 详情 | |
| (XIV) | 27665 | phenyl (1R,2S,3R,5S)-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate | C27H27NO2 | 详情 | 详情 | |
| (XV) | 27666 | (1R,2S,3R,5S)-8-methyl-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octane | C21H25N | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(III)The reaction of tropanone (I) with N,N-bis(trifluoromethylsulfonyl)aniline and sodium hexamethyldisilylazide in THF gives the enol triflate (II), which is condensed with 4-methylphenylboronic acid (III) by means of palladium tetrakis(triphenylphosphine) yielding the p-tolyltropane (IV). The hydrolysis of the methyl ester of (IV) with KOH affords the carboxylic acid (V), which is treated with diphenoxyphosphoryl azide in hot toluene to give the isocyanate (VI). The hydrolysis of (VI) in refluxing ethanol yields the tropanone (VII). By reaction of the tropanone (VII) with N,N-bis(trifluoromethylsulfonyl)aniline to give the corresponding enol triflate (IX), which is then condensed with phenylboronic acid (X) by means of Pd(Ph3)4 to give (XI), which by reaction with phenyl chloroformate in dichloromethane yields the N-carboxylate (XII). The reduction of (XII) with H2 over Pd/C in methanol affords a mixture of the (exo, exo) (XIII) and (endo, endo) (XIV) compounds, which is reduced with LiAlH4 in ethyl ether providing a mixture of the target compound and its (endo, endo) isomer (XV) that is separated by chromatography.
| 【1】 Jiang, S.; Chang, A.-C.; Abraham, P.; Kuhar, M.J.; Carroll, F.I.; Synthesis and transporter binding properties of (R)-2beta,3beta- and (R)-2alpha,3alpha-diaryltropanes. Bioorg Med Chem Lett 1998, 8, 24, 3689. |
| 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) | 27655 | methyl (1R,5S)-8-methyl-3-oxo-8-azabicyclo[3.2.1]octane-2-carboxylate | C10H15NO3 | 详情 | 详情 | |
| (II) | 27656 | methyl (1R,5S)-8-methyl-3-[[(trifluoromethyl)sulfonyl]oxy]-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate | C11H14F3NO5S | 详情 | 详情 | |
| (III) | 15540 | 4-methylphenylboronic acid; p-Tolylboronic acid | 5720-05-8 | C7H9BO2 | 详情 | 详情 |
| (IV) | 27657 | methyl (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate | C17H21NO2 | 详情 | 详情 | |
| (V) | 27658 | (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylic acid | C16H19NO2 | 详情 | 详情 | |
| (VI) | 27659 | (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-en-2-yl isocyanate | C16H18N2O | 详情 | 详情 | |
| (VII) | 27660 | (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octan-2-one | C15H19NO | 详情 | 详情 | |
| (VIII) | 27661 | (1R,5S)-8-methyl-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octan-2-ol | C21H25NO | 详情 | 详情 | |
| (IX) | 27667 | (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-en-2-yl trifluoromethanesulfonate | C16H18F3NO3S | 详情 | 详情 | |
| (X) | 16593 | Phenylboronic acid；Benzeneboronic acid;Phenylboron dihydroxide | 98-80-6 | C6H7BO2 | 详情 | 详情 |
| (XI) | 27662 | (1R,5S)-8-methyl-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]oct-2-ene | C21H23N | 详情 | 详情 | |
| (XII) | 27663 | phenyl (1R,5S)-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate | C27H25NO2 | 详情 | 详情 | |
| (XIII) | 27664 | phenyl (1R,2R,3S,5S)-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate | C27H27NO2 | 详情 | 详情 | |
| (XIV) | 27665 | phenyl (1R,2S,3R,5S)-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octane-8-carboxylate | C27H27NO2 | 详情 | 详情 | |
| (XV) | 27666 | (1R,2S,3R,5S)-8-methyl-3-(4-methylphenyl)-2-phenyl-8-azabicyclo[3.2.1]octane | C21H25N | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(II)Suzuki coupling of 3-bromo-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-one (I) with 4-methylphenylboronic acid (II) by means of palladium tetrakis(triphenylphosphine) gave (III). Subsequent refluxing of (III) with dimethyl carbonate in the presence of NaOMe afforded ketoester (IV). This was reduced with NaBH4 to give hydroxy ester (V), which was then dehydrated and hydrolyzed to the unsaturated acid (VI) with HCl in diglyme at 100 C. Alternatively, ketone (III) was carboxylated under CO2 atmosphere in the presence of either potassium carbonate or potassium tert-butoxide. The resulting ketoacid (VII) was reduced to hydroxyacid (VIII) with NaBH4, and then dehydrated to (VI) using 80% formic acid at 100 C. Carboxylic acid (VI) was then converted to the corresponding acid chloride (IX) by means of oxalyl chloride in CH2Cl2.
| 【1】 Shiraishi, M.; Aramaki, Y.; Seto, M.; et al.; Discovery of small molecule CCR5 antagonists. 19th Symp Med Chem and 8th Annu Meet Div Med Chem Jpn (Nov 17-19, Tokyo) 1999, Abst 2P-06. |
| 【2】 Kitayoshi, T.; Aramaki, Y.; Oda, T.; Honda, S.; Shiraishi, M. (Takeda Chemical Industries, Ltd.); Anilide deriv., production and use thereof. JP 1999263764; WO 9932468 . |
| 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) | 31554 | 3-bromo-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-5-one | C11H11BrO | 详情 | 详情 | |
| (II) | 15540 | 4-methylphenylboronic acid; p-Tolylboronic acid | 5720-05-8 | C7H9BO2 | 详情 | 详情 |
| (III) | 31555 | 3-(4-methylphenyl)-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-5-one | C18H18O | 详情 | 详情 | |
| (IV) | 31556 | ethyl 3-(4-methylphenyl)-5-oxo-6,7,8,9-tetrahydro-5H-benzo[a]cycloheptene-6-carboxylate | C21H22O3 | 详情 | 详情 | |
| (V) | 31557 | ethyl 5-hydroxy-3-(4-methylphenyl)-6,7,8,9-tetrahydro-5H-benzo[a]cycloheptene-6-carboxylate | C21H24O3 | 详情 | 详情 | |
| (VI) | 31560 | 2-(4-methylphenyl)-6,7-dihydro-5H-benzo[a]cycloheptene-8-carboxylic acid | C19H18O2 | 详情 | 详情 | |
| (VII) | 31558 | 3-(4-methylphenyl)-5-oxo-6,7,8,9-tetrahydro-5H-benzo[a]cycloheptene-6-carboxylic acid | C19H18O3 | 详情 | 详情 | |
| (VIII) | 31559 | 5-hydroxy-3-(4-methylphenyl)-6,7,8,9-tetrahydro-5H-benzo[a]cycloheptene-6-carboxylic acid | C19H20O3 | 详情 | 详情 | |
| (IX) | 31561 | 2-(4-methylphenyl)-6,7-dihydro-5H-benzo[a]cycloheptene-8-carbonyl chloride | C19H17ClO | 详情 | 详情 |