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【结 构 式】 
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【分子编号】13364 【品名】Benzene 【CA登记号】71-43-2 |
【 分 子 式 】C6H6 【 分 子 量 】78.11364 【元素组成】C 92.26% H 7.74% |
合成路线1
该中间体在本合成路线中的序号：(I)The Friedel-Kraft's reaction of benzene (I) and 3,4-dichlorobenzoyl chloride (II) by means of AlCl3 in dichloromethane gives 3,4-dichlorobenzophenone (III), which is condensed with diethyl succinate (IV) by means of potassium tert-butoxide in tert-butyl alcohol yielding ethyl 3-ethoxycarbonyl-4-(3,4-dichlorophenyl)-4-phenylbut-3-enoate (V). Hydrolysis of (V) with HBr in refluxing acetic acid affords 4-(3,4-dichlorophenyl)-4-phenylbut-3-enoic acid (VI), which is hydrogenated with H2 over Pd/C in ethyl acetate giving 4-(3,4-dichlorophenyl)-4-phenylbutanoic acid (VII), which is converted into the corresponding acyl chloride (VIII) with refluxing SOCl2. Cyclization of (VIII) with AlCl3 in CS2 yields 4-(3,4-dichlorophenyl)-3,4-dihydro-1-(2H)-naphthalenone (IX), which is treated with methylamine and TiCl4 in THF affording the corresponding Schiff base (X). Finally, this compound is reduced with H2 over Pd/C in THF.
| 【1】 Kraska, A.R.; Welch, W.M. Jr.; Koe, B.K.; Harbert, C.A. (Pfizer Inc.); Antidepressant derivatives of cis-4-phenyl-1,2,3,4-tetrahydro-1-naphtalenamine. EP 0030081; JP 1981086137; US 4536518 . |
| 【2】 Castaner, J.; Serradell, M.N.; Sertraline. Drugs Fut 1984, 9, 4, 277. |
| 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) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (II) | 26356 | 3,4-dichlorobenzoyl chloride | 3024-72-4 | C7H3Cl3O | 详情 | 详情 |
| (III) | 30578 | (3,4-dichlorophenyl)(phenyl)methanone | 6284-79-3 | C13H8Cl2O | 详情 | 详情 |
| (IV) | 12313 | diethyl succinate | 123-25-1 | C8H14O4 | 详情 | 详情 |
| (V) | 30579 | diethyl 2-[(Z)-(3,4-dichlorophenyl)(phenyl)methylidene]succinate | C21H20Cl2O4 | 详情 | 详情 | |
| (VI) | 30580 | (E)-4-(3,4-dichlorophenyl)-4-phenyl-3-butenoic acid | C16H12Cl2O2 | 详情 | 详情 | |
| (VII) | 30581 | 4-(3,4-dichlorophenyl)-4-phenylbutyric acid | C16H14Cl2O2 | 详情 | 详情 | |
| (VIII) | 30582 | 4-(3,4-dichlorophenyl)-4-phenylbutanoyl chloride | C16H13Cl3O | 详情 | 详情 | |
| (IX) | 30583 | 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone; 4-(3',4'-Dichlorophenyl)-1-tetralone | 79580-19-3 | C16H12Cl2O | 详情 | 详情 |
| (X) | 30584 | N-[4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]-N-methylamine; N-[4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine | C17H15Cl2N | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)A new synthesis of 13C- or 14C-labeled SKF-86466 has been described: The Friedel Craft's condensation of labeled benzene (I) with oxalyl chloride by means of AlCl3 in CS2 yields benzoic acid (II), which is chlorinated by means of cupric chloride and thallium (III) trifluoroacetate in trifluoroacetic acid to give 2-chlorobenzoic acid (III). The reduction of (III) by means of borane/THF complex in THF affords 2-chlorobenzyl alcohol (IV), which is treated with hot concentrated HCl to afford 2-chlorobenzyl chloride (V). The Grignard condensation of (V) with N-methyloxazolidine (VI) by means of Mg in ether gives N-[2-(2-chlorophenyl)ethyl]-N-methyl-2-hydroxyethylamine (VII), which is finally cyclized by treatment with PCl5 in hot trichlorobenzene followed by addition of AlCl3 and heating at 215-25 C.
| 【1】 Etzkorn, F.; Villani, A.J.; Rotert, G.A.; Heys, J.R.; Synthesis of 13C, 14C and 2H13C labeled adrenoceptor antagonists: 6-c hloro-2,3,4,5-tetrahydro-3-methyl-1H-3-benzazepine hydrochloride and its N-desmethyl analog. J Label Compd Radiopharm 1988, 25, 12, 1339. |
| 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) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (I) | 44622 | C6H6 | 详情 | 详情 | ||
| (II) | 10202 | Benzoic acid | 65-85-0 | C7H6O2 | 详情 | 详情 |
| (II) | 44623 | C7H6O2 | 详情 | 详情 | ||
| (III) | 10203 | o-Chlorobenzoic acid; 2-Chlorobenzoic acid | 118-91-2 | C7H5ClO2 | 详情 | 详情 |
| (III) | 44624 | C7H5ClO2 | 详情 | 详情 | ||
| (IV) | 10204 | 2-Chlorobenzyl alcohol; (2-Chlorophenyl)methanol | 17849-38-6 | C7H7ClO | 详情 | 详情 |
| (IV) | 44625 | C7H7ClO | 详情 | 详情 | ||
| (V) | 10205 | 1-Chloro-2-(chloromethyl)benzene; 2-Chlorobenzyl chloride | 611-19-8 | C7H6Cl2 | 详情 | 详情 |
| (V) | 44626 | C7H6Cl2 | 详情 | 详情 | ||
| (VI) | 10206 | 3-Methyl-1,3-oxazolane | C4H9NO | 详情 | 详情 | |
| (VII) | 10207 | 2-[(2-Chlorophenethyl)(methyl)amino]-1-ethanol | C11H16ClNO | 详情 | 详情 | |
| (VII) | 44627 | C11H16ClNO | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：A new synthesis of adinazolam has been described: The condensation of phthaloyl-glycyl chloride (I) with 2-amino-5-chlorobenzophenone (II) in refluxing toluene gives 4-chloro-2-(phthaloylglycylamido)benzophenone (III), which is cyclized by means of hydrazine in refluxing ethanol yielding 7-chloro-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one (IV). The reaction of (IV) with P2S5 in hot pyridine affords the corresponding thione (V), which is finally cyclized with N,N-dimethylglycine hydrazide by means of triethylamine in refluxing butanol. The starting products (I) and (II) are obtained as follows: The reaction of N-(ethoxycarbonyl)phthalimide (VI) with glycine by means of Na2CO3 in water gives the N-phthaloylglycine (VII), which is then treated with refluxing SOCl2 to give (I). The protection of 2-amino-4-chlorobenzoic acid (VIII) with tosyl chloride gives the corresponding N-tosyl derivative (IX), which by reaction with refluxing SOCl2 is converted into the acyl chloride (X). Finally, this compound is submitted to a Friedel-Craft's condensation with benzene and AlCl3 to afford (II).
| 【1】 Johnson, T.D.; Hsi, R.S.P.; Carbon-14 labeled 1,4-benzodiazepines. 3. J Label Compd Radiopharm 1976, 12, 4, 613-619. |
| 【2】 Castaner, J.; Pento, J.T.; Blancafort, P.; Serradell, M.N.; Adinazolam. Drugs Fut 1983, 8, 2, 87. |
| 【3】 Stelzer, L.S.; Hsi, R.S.P.; Synthesis of adinazolam mesylate-multiply labeled with carbon-13 and deuterium. J Label Compd Radiopharm 1989, 26, 3, 287. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 | |
| 40924 | 2-(dimethylamino)acetohydrazide | 539-64-0 | C4H11N3O | 详情 | 详情 | |
| (I) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (II) | 10279 | (2-Amino-5-chlorophenyl)(phenyl)methanone; 2-Amino-5-chlorobenzophenone | 719-59-5 | C13H10ClNO | 详情 | 详情 |
| (III) | 10280 | N-(2-Benzoyl-4-chlorophenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamide | C23H15ClN2O4 | 详情 | 详情 | |
| (IV) | 10281 | 7-Chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one; 1,4-benzdiazepin-2-one-5-phenyl-7-chloro | 1088-11-5 | C15H11ClN2O | 详情 | 详情 |
| (V) | 10282 | 7-Chloro-5-phenyl-3H-1,4-benzodiazepin-2-ylhydrosulfide; 7-Chloro-5-phenyl-3H-1,4-benzodiazepine-2-thiol | C15H11ClN2S | 详情 | 详情 | |
| (VI) | 10283 | ethyl 1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxylate; N-Carbethoxyphthalimide | 22509-74-6 | C11H9NO4 | 详情 | 详情 |
| (VII) | 10284 | N-Phthaloylglycine; 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid | 4702-13-0 | C10H7NO4 | 详情 | 详情 |
| (VIII) | 10285 | 2-Amino-5-chlorobenzoic acid | 635-21-2 | C7H6ClNO2 | 详情 | 详情 |
| (IX) | 10286 | 5-Chloro-2-[[(4-methylphenyl)sulfonyl]amino]benzoic acid | C14H12ClNO4S | 详情 | 详情 | |
| (X) | 10287 | 5-Chloro-2-[[(4-methylphenyl)sulfonyl]amino]benzoyl chloride | C14H11Cl2NO3S | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(IX)Two new syntheses of labeled azamianserin have been described: 1) [13C]-Labeled: The reaction of 2-chloropyridine-3-carbonitrile (I) with glycine ethyl ester (II) by means of Na2CO3 in DMSO gives N-(3-cyanopyridin-2-yl)glycine ethyl ester (III), which by reaction with methylamine in toluene is converted into the corresponding amide (IV). The treatment of (IV) with sodium hypophosphite and RaNi in water-acetic acid-pyridine affords N-(3-formylpyridin-2-yl)glycine methylamide (V), which is reduced with NaBH4 in methanol to the corresponding alcohol (VI). Further reduction of (VI) with LiAlH4 in refluxing dioxane gives 2-[2-(methylamino)ethylamino]-3-pyridinemethanol (VII), which is condensed with [13C]-labeled alpha-bromoacetophenone (VIII) [prepared from labeled benzene (IX) submitted to a Friedel-Crafts condensation with AlCl3 and acetic anhydride to acetophenone (X) and bromination with Br2 in ether] by means of triethylamine in dioxane to afford the substituted acetophenone (XI). The cyclization of (XI) by heating at 120 C yields the tricyclic compound (XII), which is reduced with LiAlH4 - AlCl3 in ethyl ether to give 2-(4-methyl-2-phenylpiperazin-1-yl)pyridine-3-methanol (XIII). Finally, this compound is cyclized in hot H2SO4.
| 【1】 Wieringa, J.H.; Kaspersen, F.M.; van Rooij, F.A.M.; Sperling, E.G.M.; The synthesis of ORG 3770 labelled with 3H, 13C and 14C. J Label Compd Radiopharm 1989, 27, 9, 1055. |
| 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) | 10308 | 2-Chloronicotinonitrile; 2-Chloro-3-cyanopyridine | 6602-54-6 | C6H3ClN2 | 详情 | 详情 |
| (II) | 10309 | ethyl 2-aminoacetate; Glycine ethyl ester | 459-73-4 | C4H9NO2 | 详情 | 详情 |
| (III) | 10310 | ethyl 2-[(3-cyano-2-pyridinyl)amino]acetate | C10H11N3O2 | 详情 | 详情 | |
| (IV) | 10311 | 2-[(3-Cyano-2-pyridinyl)amino]-N-methylacetamide | C9H10N4O | 详情 | 详情 | |
| (V) | 10312 | 2-[(3-Formyl-2-pyridinyl)amino]-N-methylacetamide | C9H11N3O2 | 详情 | 详情 | |
| (VI) | 10313 | 2-[[3-(Hydroxymethyl)-2-pyridinyl]amino]-N-methylacetamide | C9H13N3O2 | 详情 | 详情 | |
| (VII) | 10314 | (2-[[2-(Methylamino)ethyl]amino]-3-pyridinyl)methanol | C9H15N3O | 详情 | 详情 | |
| (VIII) | 10315 | 2-Bromo-1-phenyl-ethanone; 2-Bromo-1-phenyl-1-ethanone | 70-11-1 | C8H7BrO | 详情 | 详情 |
| (VIII) | 44642 | 2-bromo-1-phenyl-1-ethanone | C8H7BrO | 详情 | 详情 | |
| (IX) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (IX) | 44640 | benzene | C6H6 | 详情 | 详情 | |
| (X) | 10317 | Acetophenone | 98-86-2 | C8H8O | 详情 | 详情 |
| (X) | 44641 | acetophenone | C8H8O | 详情 | 详情 | |
| (XI) | 10318 | 2-[(2-[[3-(Hydroxymethyl)-2-pyridinyl]amino]ethyl)(methyl)amino]-1-phenyl-1-ethanone | C17H21N3O2 | 详情 | 详情 | |
| (XI) | 44643 | 2-[(2-[[3-(hydroxymethyl)-2-pyridinyl]amino]ethyl)(methyl)amino]-1-phenyl-1-ethanone | C17H21N3O2 | 详情 | 详情 | |
| (XII) | 10319 | 8-Methyl-6a-phenyl-7,8,9,10-tetrahydro-5H,6aH-pyrazino[2,1-b]pyrido[2,3-d][1,3]oxazine | C17H19N3O | 详情 | 详情 | |
| (XII) | 44644 | 8-methyl-6a-phenyl-7,8,9,10-tetrahydro-5H,6aH-pyrazino[2,1-b]pyrido[2,3-d][1,3]oxazine | C17H19N3O | 详情 | 详情 | |
| (XIII) | 10320 | [2-(4-Methyl-2-phenylpiperazino)-3-pyridinyl]methanol | 61337-89-1 | C17H21N3O | 详情 | 详情 |
| (XIII) | 44645 | [2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinyl]methanol | C17H21N3O | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：Protected aminopentanoic acid derivative (I) is converted into phenylpentanone (II) by first treatment with thionyl chloride in refluxing benzene, followed by condensation with benzene and aluminum chloride. Reduction of (II) with aluminum isopropoxide in refluxing isopropanol provides phenylpentanol derivative (III), which is then treated with hydrazine hydrate in refluxing EtOH to furnish 2-amino-4-methyl-1-phenylpentane-1-ol (IV). Coupling of (IV) with chloro derivative (V) at 110-120 C yields derivative (VI), which is finally converted into the desired oxazolidinone by reaction with ethyl chlorocarbonate (VII) in chloroform followed by heating in toluene and treatment with aluminum isopropoxide.
| 【1】 Moritoh, N.; Satoh, M.; Shinozaki, H.; Masaki, M.; Hashimoto, K.; Kamishiro, T. (Nippon Chemiphar Co., Ltd.); 1,3-Oxazolidin-2-one derivs.. CH 663207; DE 3519261; ES 8800571; ES 8802152; FR 2571052; GB 2165237; JP 1986083170; US 4644063 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 | |
| (I) | 50833 | (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-methylpentanoic acid | C14H15NO4 | 详情 | 详情 | |
| (II) | 50834 | 2-[(1S)-1-benzoyl-3-methylbutyl]-1H-isoindole-1,3(2H)-dione | C20H19NO3 | 详情 | 详情 | |
| (III) | 50835 | 2-[(1S)-1-[(R)-hydroxy(phenyl)methyl]-3-methylbutyl]-1H-isoindole-1,3(2H)-dione | C20H21NO3 | 详情 | 详情 | |
| (IV) | 50836 | (1R,2S)-2-amino-4-methyl-1-phenyl-1-pentanol | C12H19NO | 详情 | 详情 | |
| (V) | 50837 | 1-(3-chloropropyl)azepane | C9H18ClN | 详情 | 详情 | |
| (VI) | 50838 | (1R,2S)-2-[[3-(1-azepanyl)propyl]amino]-4-methyl-1-phenyl-1-pentanol | C21H36N2O | 详情 | 详情 | |
| (VII) | 11229 | 1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate | 541-41-3 | C3H5ClO2 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(A)The reaction of pimelic acid monoester (I) with refluxing SOCl2 gives the corresponding acid chloride (II), which by a Friedel-Craft's condensation with benzene (AlCl3 as catalyst) is converted into 6-benzoylhexanoic acid ethyl ester (III). The reduction of (III) with NaBH4 in methanol affords 7-hydroxy-7-phenylheptanoic acid ethyl ester (IV), which is hydrolyzed with NaOH in hot THF - water to yield the corresponding free acid (V). Finally, this compound is condensed with trimethylhydroquinone (VI) by means of boron trifluoride ethearate in hot toluene.
| 【1】 Terao, S.; Maki, Y. (Takeda Chemical Industries, Ltd.); Quinone amides, their production and use. EP 0232089; JP 1987246545 . |
| 【2】 Terao, S.; Maki, Y. (Takeda Chemical Industries, Ltd.); Quinone derivs., their production and use. AU 8545615; EP 0171251; ES 8704870; JP 1986044840; JP 1991072444; JP 1991081248; JP 1991086841; US 5180742; WO 8600887; WO 8604058 . |
| 【3】 Shiraishi, M.; Kato, K.; Terao, S.; Ashida, Y.; Terashita, Z.-I.; Kito, G.; Quinones. 4. Novel eicosanoid antagonists: Synthesis and pharmacological evaluation. J Med Chem 1989, 32, 9, 2214-21. |
| 【4】 Terao, S.; Quinone derivatives: Synthesis and structure-activity relations of a novel class of eicosanoid antagonists, AA-2414 and its analogs. Advances in Prostaglandin, Thromboxane and Leukotriene Research 1989, 19, 651-654. |
| 【5】 Prous, J.; Castaner, J.; AA-2414. Drugs Fut 1990, 15, 8, 783. |
| 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) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (I) | 31145 | 7-ethoxy-7-oxoheptanoic acid | 33018-91-6 | C9H16O4 | 详情 | 详情 |
| (II) | 31146 | ethyl 7-chloro-7-oxoheptanoate | 14794-32-2 | C9H15ClO3 | 详情 | 详情 |
| (III) | 31147 | ethyl 7-oxo-7-phenylheptanoate | C15H20O3 | 详情 | 详情 | |
| (IV) | 31148 | ethyl 7-hydroxy-7-phenylheptanoate | C15H22O3 | 详情 | 详情 | |
| (V) | 31149 | 7-hydroxy-7-phenylheptanoic acid | C13H18O3 | 详情 | 详情 | |
| (VI) | 26357 | 2,3,5-trimethyl-1,4-benzenediol | 700-13-0 | C9H12O2 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(A)By reaction of ethyl 2-fluoro-4-biphenylylacetate (I) first with diethyl carbonate and sodium ethoxide, and then with dimethyl sulfate in ethanol to give diethyl 2-fluoro-4-biphenylyl-alpha-methylmalonate (II), which was hydrolyzed with NaOH in ethanol and finally decarboxylated at 180-200 C. The starting product (I) was obtained as follows: the Ullman condensation of 4-bromo-3-nitroacetophenone (III) gives 2-nitro-4-acetylbiphenyl (IV), which was reduced to the corresponding amino compound (V). This, by the Schieman reaction was converted into 2-fluoro-4-acetylbiphenyl (VI), which by heating with sulfur and morpholine (B) gave 2-fluoro-4-biphenylylacetic acid (VII), and finally (VII) was esterified by refluxing with ethanol and H2SO4.
| 【1】 Adams, S.S.; et al.; 2-(Mono- and difluoro-4-biphenyl)propionic acids. US 3755427 . |
| 【2】 Thorpe, P.; Castaner, J.; Flurbiprofen. Drugs Fut 1976, 1, 7, 323. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
| (A) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (I) | 34107 | ethyl 2-(2-fluoro[1,1'-biphenyl]-4-yl)acetate | C16H15FO2 | 详情 | 详情 | |
| (II) | 34108 | diethyl 2-(2-fluoro[1,1'-biphenyl]-4-yl)-2-methylmalonate | C20H21FO4 | 详情 | 详情 | |
| (III) | 34109 | 1-(4-bromo-3-nitrophenyl)-1-ethanone | 18640-58-9 | C8H6BrNO3 | 详情 | 详情 |
| (IV) | 34110 | 1-(2-nitro[1,1'-biphenyl]-4-yl)-1-ethanone | C14H11NO3 | 详情 | 详情 | |
| (V) | 34111 | 1-(2-amino[1,1'-biphenyl]-4-yl)-1-ethanone | C14H13NO | 详情 | 详情 | |
| (VI) | 34112 | 1-(2-fluoro[1,1'-biphenyl]-4-yl)-1-ethanone | C14H11FO | 详情 | 详情 | |
| (VII) | 34113 | 2-(2-fluoro[1,1'-biphenyl]-4-yl)acetic acid | C14H11FO2 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(XI)Synthesis of [14C]-labeled CI-980: The reaction of N-(ethoxycarbonyl)-L-alanine (VII) with N-methoxy-N-methylamine (VIII) by means of carbonyldiimidazole (CDI) in THF/dichloromethane gives the corresponding amide (IX), which is treated with phenylmagnesium bromide (1 mol) yielding the bromomagnesium salt (X). The bromination of [14C]-labeled benzene (XI) with Br2/HBr/H2O2 gives the labeled bromobenzene (XII), which is converted into the corresponding Grignard reagent (XIII) by reaction with Mg and dibromoethane in ether. The reaction of the previously obtained magnesium salt of alaninamide (X) with the labeled Grignard reagent (XIII) affords the labeled carbamate (XIV), which is reduced with NaBH4 in methanol and treated with KOH giving a mixture of the oxazolidinone (XV) and the aminoalcohol (XVI), separated by acidic extraction. The hydrolysis of the oxazolidinone (XV) with KOH yielded the desired aminoalcohol (XVI). The aminoalcohol (XVI) by means of triethylamine in refluxing ethanol gives (1S,2R)-N-[2-amino-4-(2-hydroxy-1-methyl-2-phenylethylamino)-3-nitropyridin-6-yl]carbamic acid ethyl ester (XVII), which is oxidized with CrO3-pyridine in dichloromethane yielding the corresponding ketone (XVIII). The reductocyclization of (XVIII) with H2 over RaNi in glacial acetic acid affords the free base of title compound (XIX), which is finally treated with 2-hydroxyethanesulfonic acid in methanol.
| 【1】 Graul, A.; Martell, A.M.; Castaner, J.; Mivobulin Isethionate. Drugs Fut 1997, 22, 9, 980. |
| 【2】 Woo, P.W.K.; Lee, H.T.; Synthesis of [14C]CI-980, ethyl [5-amino-1,2-dihydro-2(S)-methyl-3-[14C]phenylpyrido[3,4-b]pyrazin-7 -yl]carbamate isethionate salt, a tubulin-binding, antimitotic, broad-spectrum antitumor agent. J Label Compd Radiopharm 1994, 34, 1, 1-10. |
| 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) | 13359 | 2-Hydroxy-1-ethanesulfonic acid | 107-36-8 | C2H6O4S | 详情 | 详情 |
| (VII) | 13360 | (2S)-2-[(Ethoxycarbonyl)amino]propionic acid | C6H11NO4 | 详情 | 详情 | |
| (VIII) | 13361 | (Methoxyamino)methane; N,O-Dimethylhydroxylamine | 1117-97-1 | C2H7NO | 详情 | 详情 |
| (IX) | 13358 | ethyl (2S)-5-amino-2-methyl-3-phenyl-1,2-dihydropyrido[3,4-b]pyrazin-7-ylcarbamate | C17H19N5O2 | 详情 | 详情 | |
| (IX) | 13362 | ethyl (1S)-2-[methoxy(methyl)amino]-1-methyl-2-oxoethylcarbamate | C8H16N2O4 | 详情 | 详情 | |
| (X) | 13363 | N-(Ethoxycarbonyl)-N-[1(S)-(N-methoxy-N-methylcarbamoyl)ethyl]amide anion | C8H15N2O4 | 详情 | 详情 | |
| (XI) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (XI) | 44622 | C6H6 | 详情 | 详情 | ||
| (XII) | 13365 | Monobromobenzene; 1-Bromobenzene；Phenylbromide;bromobenzene | 108-86-1 | C6H5Br | 详情 | 详情 |
| (XII) | 45166 | C6H5Br | 详情 | 详情 | ||
| (XIII) | 17616 | bromo(phenyl)magnesium; Phenyl Magnesium Bromide | 100-58-3 | C6H5BrMg | 详情 | 详情 |
| (XIII) | 45167 | C6H5BrMg | 详情 | 详情 | ||
| (XIV) | 13367 | ethyl (1S)-1-methyl-2-oxo-2-phenylethylcarbamate | C12H15NO3 | 详情 | 详情 | |
| (XIV) | 45168 | C12H15NO3 | 详情 | 详情 | ||
| (XV) | 13368 | (4S)-4-Methyl-5-phenyl-1,3-oxazolidin-2-one; (4S,5R)-(-)-4-Methyl-5-phenyl-2-oxazolidinone | 16251-45-9 | C10H11NO2 | 详情 | 详情 |
| (XV) | 45169 | C9H13NO | 详情 | 详情 | ||
| (XVI) | 13355 | 2-Amino-1-phenyl-1-propanol; (1S,2R)-(+)-Norephedrine | 37577-28-9 | C9H13NO | 详情 | 详情 |
| (XVI) | 45170 | C10H11NO2 | 详情 | 详情 | ||
| (XVII) | 13356 | ethyl 6-amino-4-[[(1S,2R)-2-hydroxy-1-methyl-2-phenylethyl]amino]-5-nitro-2-pyridinylcarbamate | C17H21N5O5 | 详情 | 详情 | |
| (XVII) | 63746 | C17H21N5O5 | 详情 | 详情 | ||
| (XVIII) | 13357 | ethyl 6-amino-4-[[(1S)-1-methyl-2-oxo-2-phenylethyl]amino]-5-nitro-2-pyridinylcarbamate | C17H19N5O5 | 详情 | 详情 | |
| (XVIII) | 63747 | C17H19N5O5 | 详情 | 详情 | ||
| (XIX) | 63748 | C17H19N5O2 | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(I)The syntheses of remacemide [13C]-, [14C]-, [2H]-,and [3H]-labeled in several different positions have been described: The Friedel Crafts condensation of benzene with acetyl chloride (II) by means of AlCl3 in CS2 gives acetophenone (III), which by a Grignard condensation with benzylmagnesium chloride (IV) in THF yields 1,2-diphenyl-3-propanol (V). Reaction of (V) with NaCN and sulfuric acid in acetic acid affords the formamide (VI), which is hydrolyzed with refluxing aqueous HCl to give the amine (VII). The condensation of (VII) with N-Boc-glycine (VIII) and DCC or with the N-Boc-glycine mixed anhydride (IX) and TEA in dichloromethane yields the protected glycinamide (X), which is finally deprotected with HCl in refluxing methanol. Alternatively, condensation of amine (VII) with chloroacetyl chloride (XI) by means of pyridine in dichloromethane provides the chloroacetamide (XII), which is finally treated with ammonia in ethanol/dichloromethane. In this reaction sequence, the use of [carbonyl-14C]-acetophenone (III), [13C6]-benzene (I), [13C2]-acetyl chloride (II), the [1-13C]-glycines (VIII) and (IX) or the [2-3H]-glycine (VIII) as starting materials affords remacemide labeled in the corresponding positions. [2H or 3H]-remacemide labeled in 2,6-positions of the 1-phenyl ring is obtained by submitting the amine (VII) to isotopic exchange with 2H2O/RhCl3, 2H2/Iridium complex, or 3H2/Iridium complex.
| 【1】 Dawson, G.E.; Coombs, M.E.; Fedorchuk, M.; et al.; Preparation of remacemide hydrochloride labelled with carbon-14, carbon-13, deuterium and tritium. J Label Compd Radiopharm 2000, 43, 6, 533. |
| 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) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (II) | 19273 | acetyl chloride | 75-36-5 | C2H3ClO | 详情 | 详情 |
| (III) | 10317 | Acetophenone | 98-86-2 | C8H8O | 详情 | 详情 |
| (IV) | 18327 | benzyl(chloro)magnesium | 6921-34-2 | C7H7ClMg | 详情 | 详情 |
| (V) | 41763 | 1,2-diphenyl-2-propanol | 5342-87-0 | C15H16O | 详情 | 详情 |
| (VI) | 41764 | 1-methyl-1,2-diphenylethylformamide | C16H17NO | 详情 | 详情 | |
| (VII) | 41765 | 1-methyl-1,2-diphenylethylamine; 1,2-diphenyl-2-propanamine | C15H17N | 详情 | 详情 | |
| (VIII) | 18066 | N-alpha-t-BOC-glycine; 2-[(tert-butoxycarbonyl)amino]acetic acid | 4530-20-5 | C7H13NO4 | 详情 | 详情 |
| (IX) | 41766 | [(tert-butoxycarbonyl)amino]acetic 1,1-dimethylpropionic anhydride | C12H21NO5 | 详情 | 详情 | |
| (X) | 41767 | tert-butyl 2-[(1-methyl-1,2-diphenylethyl)amino]-2-oxoethylcarbamate | C22H28N2O3 | 详情 | 详情 | |
| (XI) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
| (XII) | 41768 | 2-chloro-N-(1-methyl-1,2-diphenylethyl)acetamide | C17H18ClNO | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(I)A synthesis of [14C]-labeled SR-57746A has been described: The iodination of [14C6]-benzene (I) with nitric acid/I2 gives iodobenzene (II), which is treated with sodium trifluoroacetate and CuI yielding trifluoromethylbenzene (III). The nitration of (III) with sodium nitrate affords 3-(trifluoromethyl)nitrobenzene (IV), which is reduced with Fe/HCl to the corresponding aniline (V). The reaction of (V) with tert-butyl nitrite and CuBr2 provides 3-(trifluoromethyl)bromobenzene (VI), which is treated with Mg in THF affording the corresponding Grignard reagent (VII). The condensation of (VII) with piperidone (VIII) gives the piperidol (IX), which is finally dehydrated in acidic medium. In order to aviod radioactive contamination during the purification of compounds iodobenzene (II) and trifluoromethylbenzene (III) by liquid chromatography, a safer route using less volatile compounds has been developed: The nitration of [14C6]-benzene (I) with nitric acid gives nitrobenzene (X), which is iodinated with IPy2BF4/CF3SO3H yielding 3-iodonitrobenzene (XI). Finally, this compound is trifluoromethylated with CF3SiMe3, CuI and KF to provide 3-(trifluoromethyl)nitrobenzene (IV) already reported.
| 【1】 Robic, N.; Noel, J.P.; Synthesis of [trifluoromethyl-[C-14(6)]-phenyl] SR 57746A. J Label Compd Radiopharm 1999, 42, 2, 109. |
| 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) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (I) | 45201 | benzene | C6H6 | 详情 | 详情 | |
| (II) | 26344 | 1-Iodobenzene | 591-50-4 | C6H5I | 详情 | 详情 |
| (II) | 45202 | 1-iodobenzene | C6H5I | 详情 | 详情 | |
| (III) | 26345 | 1-(Trifluoromethyl)benzene | 98-08-8 | C7H5F3 | 详情 | 详情 |
| (III) | 45203 | 1-(trifluoromethyl)benzene | C7H5F3 | 详情 | 详情 | |
| (IV) | 26346 | 1-nitro-3-(trifluoromethyl)benzene | 98-46-4 | C7H4F3NO2 | 详情 | 详情 |
| (IV) | 45204 | 1-nitro-3-(trifluoromethyl)benzene | C7H4F3NO2 | 详情 | 详情 | |
| (V) | 26347 | 3-(trifluoromethyl)phenylamine; 3-(trifluoromethyl)aniline; 3-aminobenzotrifluoride | 98-16-8 | C7H6F3N | 详情 | 详情 |
| (V) | 45205 | 3-(trifluoromethyl)phenylamine; 3-(trifluoromethyl)aniline | C7H6F3N | 详情 | 详情 | |
| (VI) | 26348 | 1-bromo-3-(trifluoromethyl)benzene; 3-Bromobenzotrifluoride | 401-78-5 | C7H4BrF3 | 详情 | 详情 |
| (VI) | 45206 | 1-bromo-3-(trifluoromethyl)benzene | C7H4BrF3 | 详情 | 详情 | |
| (VII) | 12028 | Bromo[3-(trifluoromethyl)phenyl]magnesium | 402-26-6 | C7H4BrF3Mg | 详情 | 详情 |
| (VII) | 45207 | bromo[3-(trifluoromethyl)phenyl]magnesium | C7H4BrF3Mg | 详情 | 详情 | |
| (VIII) | 26349 | 1-[2-(2-naphthyl)ethyl]-4-piperidinone | C17H19NO | 详情 | 详情 | |
| (IX) | 26350 | 1-[2-(2-naphthyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-4-piperidinol | C24H24F3NO | 详情 | 详情 | |
| (IX) | 45208 | 1-[2-(2-naphthyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-4-piperidinol | C24H24F3NO | 详情 | 详情 | |
| (X) | 22523 | 1-nitrobenzene | 28250-14-8 | C6H5NO2 | 详情 | 详情 |
| (X) | 45209 | 1-nitrobenzene | C6H5NO2 | 详情 | 详情 | |
| (XI) | 26352 | 3-Iodonitrobenzene; 1-iodo-3-nitrobenzene | 645-00-1 | C6H4INO2 | 详情 | 详情 |
| (XI) | 45210 | 1-iodo-3-nitrobenzene | C6H4INO2 | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(VII)Pentadeuterated saquinavir: The nitration of hexadeuterobenzene (VII) with HNO3/H2SO4 gives pentadeuteronitrobenzene (VIII), which is hydrogenated with deuterium/Pt in D1-methanol yielding heptadeuteroaniline (IX). The cyclization of (IX) with crotonic aldehyde (II) by means of DCI/D2O and acetic anhydride as before affords hexadeuterated quinoline (X), which is brominated with Br2 as before giving the tribromo derivative (XI). The hydrolysis of (XI) with sulfuric acid as before yields the acid (XII), which is finally condensed with Ro-32-0445 (VI) as before.
| 【1】 Wiltshire, H.R.; et al.; The synthesis of labelled forms of saquinavir. J Label Compd Radiopharm 1998, 41, 12, 1103. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 22517 | (E)-2-butenal | 4170-30-3 | C4H6O | 详情 | 详情 |
| (VI) | 22521 | (2S)-N(1)-[(1S,2R)-3-[(3S,4aS,8aS)-3-[(tert-butylamino)carbonyl]octahydro-2(1H)-isoquinolinyl]-1-benzyl-2-hydroxypropyl]-2-aminobutanediamide | C28H45N5O4 | 详情 | 详情 | |
| (VII) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (VII) | 63831 | benzene | C6H6 | 详情 | 详情 | |
| (VIII) | 22523 | 1-nitrobenzene | 28250-14-8 | C6H5NO2 | 详情 | 详情 |
| (VIII) | 63832 | 1-nitrobenzene | C6H5NO2 | 详情 | 详情 | |
| (IX) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (IX) | 63833 | aniline; phenylamine | C6H7N | 详情 | 详情 | |
| (X) | 13161 | Quinaldine; 2-Methylquinoline | 91-63-4 | C10H9N | 详情 | 详情 |
| (X) | 63834 | 2-methylquinoline | C10H9N | 详情 | 详情 | |
| (XI) | 22526 | 2-(tribromomethyl)quinoline | 613-53-6 | C10H6Br3N | 详情 | 详情 |
| (XI) | 63835 | 2-(tribromomethyl)quinoline | C10H6Br3N | 详情 | 详情 | |
| (XII) | 14532 | 2-Quinolinecarboxylic acid; Quinaldic Acid | 93-10-7 | C10H7NO2 | 详情 | 详情 |
| (XII) | 63836 | 2-quinolinecarboxylic acid | C10H7NO2 | 详情 | 详情 |
合成路线12
该中间体在本合成路线中的序号：(XXI)5)[15N,13C,2H]-Saquinavir: The nitration of [13C6]-benzene (XXI) with [15N]-nitric acid gives the corresponding nitrobenzene (XXII), which is reduced with Sn/HCl to the aniline (XXIII). The cyclization of (XXIII) with crotonic aldehyde (II) by means of ClD/D2O and acetic ahydride yields the tetradeuterated quinoline (XXIV), which is brominated as before givig the tribromo derivative (XXV). The hydrolysis of (XXV) with sulfuric acid as usual affords the [15N,13C6,2H3]-labeled quinoline-2-carboxylic acid (XXVI), which is finally condensed with Ro-32-0445 (VI) by means of HOBT and CDI as indicated.
| 【1】 Wiltshire, H.R.; et al.; The synthesis of labelled forms of saquinavir. J Label Compd Radiopharm 1998, 41, 12, 1103. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 22517 | (E)-2-butenal | 4170-30-3 | C4H6O | 详情 | 详情 |
| (VI) | 22521 | (2S)-N(1)-[(1S,2R)-3-[(3S,4aS,8aS)-3-[(tert-butylamino)carbonyl]octahydro-2(1H)-isoquinolinyl]-1-benzyl-2-hydroxypropyl]-2-aminobutanediamide | C28H45N5O4 | 详情 | 详情 | |
| (XI) | 22526 | 2-(tribromomethyl)quinoline | 613-53-6 | C10H6Br3N | 详情 | 详情 |
| (XI) | 45225 | 2-(tribromomethyl)quinoline | C10H6Br3N | 详情 | 详情 | |
| (XII) | 14532 | 2-Quinolinecarboxylic acid; Quinaldic Acid | 93-10-7 | C10H7NO2 | 详情 | 详情 |
| (XII) | 45226 | 2-quinolinecarboxylic acid | C10H7NO2 | 详情 | 详情 | |
| (XXI) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (XXI) | 22536 | benzene | C6H6 | 详情 | 详情 | |
| (XXII) | 22523 | 1-nitrobenzene | 28250-14-8 | C6H5NO2 | 详情 | 详情 |
| (XXII) | 22537 | 1-nitrobenzene | C6H5NO2 | 详情 | 详情 | |
| (XXIII) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (XXIII) | 22538 | phenylamine; aniline | C6H7N | 详情 | 详情 | |
| (XXIV) | 13161 | Quinaldine; 2-Methylquinoline | 91-63-4 | C10H9N | 详情 | 详情 |
| (XXIV) | 45224 | 2-methylquinoline | C10H9N | 详情 | 详情 |
合成路线13
该中间体在本合成路线中的序号：(XII)1) The reduction of 2-methyl-2-phenylpropionic acid with LiAlH4 in THF gives 2-methyl-2-phenyl-1-propanol (II), which is acetylated with acetic anhydride in pyridine yielding the acetate (III). The Friedel-Crafts condensation of (III) with 4-chlorobutyryl chloride (IV) by means of AlCl3 in dichloromethane affords the butyrophenone (V), which is condensed with alpha,alpha-diphenylipiperidine-4-methanol (VI) by means of KHCO3 and KI in refluxing toluene/water to give the butyrophenone (VII). The deacetylation of (VII) with NaOH in refluxing methanol yields the primary alcohol (VIII), which is oxidized with oxalyl chloride and DMSO in methylene chloride to the corresponding aldehyde (IX). The oxidation of (IX) with KMnO4 in acetone affords the ketoacid (X), which is finally reduced with NaBH4 in water. 2) The acetate (III) can also be obtained by Friedel-Crafts condensation of 2-methyl-2-propenyl acetate (XI) with refluxing benzene (XII) by means of AlCl3. 3) The ketoacid (X) can also be obtained by direct oxidation of the primary alcohol (VIII) with H5IO6 in chloroform/acetonitrile, or K2S2O8 in acetone/acetonitrile, both catalyzed by RuCl3.5H2O.
| 【1】 Graul, A.; Castañer, J.; Fexofenadine Hydrochloride. Drugs Fut 1996, 21, 10, 1017. |
| 【2】 King, C.-H.; Kaminski, M.A. (Merrell Pharmaceuticals, Inc.); 4-Diphenylmethyl piperidine derivs. and process for their preparation. JP 1996502022; WO 9321156 . |
| 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) | 17173 | 2-Methyl-2-phenylpropionic acid; 2-Methyl-2-phenyl-propionic acid | 826-55-1 | C10H12O2 | 详情 | 详情 |
| (II) | 17174 | 2-methyl-2-phenyl-1-propanol | C10H14O | 详情 | 详情 | |
| (III) | 17175 | 2-methyl-2-phenylpropyl acetate | 2901-13-5 | C12H16O2 | 详情 | 详情 |
| (IV) | 11265 | 4-Chlorobutanoyl chloride; 4-Chlorobutyric acid chloride | 4635-59-0 | C4H6Cl2O | 详情 | 详情 |
| (V) | 17177 | 2-[4-(4-chlorobutanoyl)phenyl]-2-methylpropyl acetate | C16H21ClO3 | 详情 | 详情 | |
| (VI) | 17178 | diphenyl(4-piperidinyl)methanol; alpha,alpha-Diphenyl-4-piperidinomethanol; Azacyclonol | 115-46-8 | C18H21NO | 详情 | 详情 |
| (VII) | 17179 | 2-[4-(4-[4-[hydroxy(diphenyl)methyl]-1-piperidinyl]butanoyl)phenyl]-2-methylpropyl acetate | 76811-96-6 | C34H41NO4 | 详情 | 详情 |
| (VIII) | 17180 | 1-[4-(2-hydroxy-1,1-dimethylethyl)phenyl]-4-[4-[hydroxy(diphenyl)methyl]-1-piperidinyl]-1-butanone | C32H39NO3 | 详情 | 详情 | |
| (IX) | 17181 | 2-[4-(4-[4-[hydroxy(diphenyl)methyl]-1-piperidinyl]butanoyl)phenyl]-2-methylpropanal | C32H37NO3 | 详情 | 详情 | |
| (X) | 17182 | 2-[4-(4-[4-[hydroxy(diphenyl)methyl]-1-piperidinyl]butanoyl)phenyl]-2-methylpropionic acid | 76811-98-8 | C32H37NO4 | 详情 | 详情 |
| (XI) | 17183 | 2-methyl-2-propenyl acetate；methallyl acetate | 820-71-3 | C6H10O2 | 详情 | 详情 |
| (XII) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (XIV) | 17609 | ethyl 2-methyl-2-phenylpropanoate | C12H16O2 | 详情 | 详情 | |
| (XV) | 17610 | ethyl 2-[4-(cyclopropylcarbonyl)phenyl]-2-methylpropanoate | C16H20O3 | 详情 | 详情 | |
| (XVI) | 17611 | ethyl 2-[4-(4-chlorobutanoyl)phenyl]-2-methylpropanoate | C16H21ClO3 | 详情 | 详情 | |
| (XVII) | 17612 | ethyl 2-[4-(4-[4-[hydroxy(diphenyl)methyl]-1-piperidinyl]butanoyl)phenyl]-2-methylpropanoate | C34H41NO4 | 详情 | 详情 | |
| (XVIII) | 17613 | ethyl 2-[4-(1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]-1-piperidinyl]butyl)phenyl]-2-methylpropanoate | C34H43NO4 | 详情 | 详情 |
合成路线14
该中间体在本合成路线中的序号：(II)Ketone (III) was prepared by Friedel-Crafts acylation of benzene (II) with 6-chloronicotinyl chloride (I). Horner-Emmons reaction of (III) with diethyl (N-methylcarbamoylmethyl)phosphonate (IV) using potassium hexamethyl-disilazide produced a 3:1 mixture of E (V) and Z olefins (VI). The desired E isomer (V) was isolated by column chromatography and then treated with bromoketone (VII) to afford the betaine (VIII). Finally, the target imidazopyridine was obtained by condensation of (VIII) with cyanamide in the presence of K2CO3.
| 【1】 Alvarez-Builla, J.; Ezquerra, J.; Vega, J.A.; Vaquero, J.J.; Hamdouchi, C.; Heinz, B.A.; Short synthesis and anti-rhinoviral activity of imidazo[1,2-a]pyridines: The effect of acyl groups at 3-position. Bioorg Med Chem Lett 1999, 9, 10, 1391. |
| 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) | 30256 | 6-chloronicotinoyl chloride | 58757-38-3 | C6H3Cl2NO | 详情 | 详情 |
| (II) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (III) | 30257 | (6-chloro-3-pyridinyl)(phenyl)methanone | C12H8ClNO | 详情 | 详情 | |
| (IV) | 30262 | diethyl 2-(methylamino)-2-oxoethylphosphonate | C7H16NO4P | 详情 | 详情 | |
| (V) | 30807 | (E)-3-(6-chloro-3-pyridinyl)-N-methyl-3-phenyl-2-propenamide | C15H13ClN2O | 详情 | 详情 | |
| (VI) | 30808 | (Z)-3-(6-chloro-3-pyridinyl)-N-methyl-3-phenyl-2-propenamide | C15H13ClN2O | 详情 | 详情 | |
| (VII) | 30809 | 1-bromo-3,3-dimethyl-2-butanone | 5469-26-1 | C6H11BrO | 详情 | 详情 |
| (VIII) | 30810 | 1-[2-Chloro-5-[2-(N-metylcarbamoyl)-1-phenylvinyl]pyridinium-1-yl]-3,3-dimethyl-2-oxo-1-butanide | C21H23ClN2O2 | 详情 | 详情 |