|
【结 构 式】 
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【分子编号】20697 【品名】3-fluoroaniline; 3-fluorophenylamine 【CA登记号】372-19-0 |
【 分 子 式 】C6H6FN 【 分 子 量 】111.1187832 【元素组成】C 64.85% H 5.44% F 17.1% N 12.61% |
合成路线1
该中间体在本合成路线中的序号：(III)The starting 3-fluorothiophenol (I) is obtained either from 3-fluoro-1-bromobenzene (II) by reaction with Mg and a following treatment with S, or from 3-fluoroaniline (III) by the Leuckart method via 3-fluorobenzenediazonium xanthate and 3-fluorophenyl xanthate. Two different ways were described for obtaining the acid (VI): 1) Reaction of (I) with 5-chloro-2-iodobenzoic acid (A) in a boiling aqueous KOH solution in the presence of Cu, which leads to the acid (IV). This is transformed in three steps (reduction with sodium dihydrodibis(2-methoxyethoxy)aluminate, followed by reaction with SOCl2 in pyridine, and final reaction with NaCN in boiling aqueous ethanol) to the nitrile (V), which is hydrolyzed with a boiling solution of KOH in aqueous ethanol. 2) Reaction of (I) with 2,5-dichloro acetophenone (B) in dimethylformamide at 150 C in the presence of Cu. The resulting ketone (VII) is proceased by the Kindler's modification of the Willgerodt reaction: treatment with S in boiling morpholine (C) gives the thiomorpholide (VIII), which is hydrolyzed either with a boiling ethanolic KOH solution or with a refluxing mixture of dilute H2SO4 and acetic acid. The acid (VI), obtained by both routes, is cyclized with polyphosphoric acid at 150 C to the ketone (IX), which is reduced with sodium borohydride in aqueous ethanol to the alcohol (X). Treatment with HCl in benzene in the presence of CaCl2 affords the reactive chloride (XI), which can be converted to the final product (XIV) by two methods: (b) substitution reaction of (XI) with 1-(ethoxycarbonyl)piperazine (D), followed by alkaline hydrolysis of the carbamate (XII) and addition of the secondary amine (XIII) to acrylamide in tert-butyl alcohol in the presence of benzyltriethylammonium hydroxide. (a) substitution reaction with 3-(1-piperazinyl)propionamide (E) in boiling chloroform gives directly (XIV);
| 【1】 Rand, K.H.; Houck, H.; Coll Czech Chem Commun 1975, 40, 2887. |
| 【2】 Nagaoka, M.R.; et al.; Coll Czech Chem Commun 1968, 33, 1852. |
| 【3】 Coll Czech Chem Commun 1978, 43, 1276. |
| 【4】 Parola, M.; Robino, G.; Pastacaldi, S.; Gentilini, P.; Pinzani, M.; Marra, F.; Coll Czech Chem Commun 1986, 51, 2598. |
| 【5】 Yu, D.; Mortin, L.I.; Zhang, X.; Alder, J.; Li, T.; Coll Czech Chem Commun 1967, 32, 2021. |
| 【6】 Ghiro, L.; et al.; Z Physik Chem (Leipzig) 1931, 156 A, 3, 397. |
| 【7】 Pomykácek, J.; Diabac, A.; Protiva, M.; Valchár, M.; Jilek, J.; Cervena, I. (SPOFA - United Pharmaceutical Works); N-Substd.-2-chloro-7-fluoro-10-piperazino-10, 11-dihydrobenzo[b,f]thiepins and acid addition salts thereof. EP 0189310; JP 1986204181; US 4678788 . |
| 【8】 Protiva, M.; VUFB-15496. Drugs Fut 1987, 12, 7, 636. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (F) | 10851 | Acrylamide | 79-06-1 | C3H5NO | 详情 | 详情 |
| (D) | 24694 | N-ethoxycarbonylpiperidine; Ethyl 1-piperazinecarboxylate; N-Ethoxycarbonyl piperazine; N-Carbethoxy piperazine | 120-43-4 | C7H14N2O2 | 详情 | 详情 |
| (A) | 28004 | 5-chloro-2-iodobenzoic acid | 13421-00-6 | C7H4ClIO2 | 详情 | 详情 |
| (B) | 28005 | 1-(2,5-dichlorophenyl)-1-ethanone | 2476-37-1 | C8H6Cl2O | 详情 | 详情 |
| (E) | 28016 | 3-(1-piperazinyl)propanamide | C7H15N3O | 详情 | 详情 | |
| (I) | 28003 | 3-fluorobenzenethiol | 2557-77-9 | C6H5FS | 详情 | 详情 |
| (II) | 28002 | 1-bromo-3-fluorobenzene; 3-Bromofluorobenzene | 1073-06-9 | C6H4BrF | 详情 | 详情 |
| (III) | 20697 | 3-fluoroaniline; 3-fluorophenylamine | 372-19-0 | C6H6FN | 详情 | 详情 |
| (IV) | 28006 | 5-chloro-2-[(3-fluorophenyl)sulfanyl]benzoic acid | C13H8ClFO2S | 详情 | 详情 | |
| (V) | 28007 | 2-[5-chloro-2-[(3-fluorophenyl)sulfanyl]phenyl]acetonitrile | C14H9ClFNS | 详情 | 详情 | |
| (VI) | 28008 | 2-[5-chloro-2-[(3-fluorophenyl)sulfanyl]phenyl]acetic acid | C14H10ClFO2S | 详情 | 详情 | |
| (VII) | 28009 | 1-[5-chloro-2-[(3-fluorophenyl)sulfanyl]phenyl]-1-ethanone | C14H10ClFOS | 详情 | 详情 | |
| (VIII) | 28010 | 2-[5-chloro-2-[(3-fluorophenyl)sulfanyl]phenyl]-1-(4-morpholinyl)-1-ethanethione | C18H17ClFNOS2 | 详情 | 详情 | |
| (IX) | 28011 | 2-chloro-7-fluorodibenzo[b,f]thiepin-10(11H)-one | C14H8ClFOS | 详情 | 详情 | |
| (X) | 28012 | 2-chloro-7-fluoro-10,11-dihydrodibenzo[b,f]thiepin-10-ol | C14H10ClFOS | 详情 | 详情 | |
| (XI) | 28013 | 2,10-dichloro-7-fluoro-10,11-dihydrodibenzo[b,f]thiepine | C14H9Cl2FS | 详情 | 详情 | |
| (XII) | 28014 | ethyl 4-(2-chloro-7-fluoro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)-1-piperazinecarboxylate | C21H22ClFN2O2S | 详情 | 详情 | |
| (XIII) | 28015 | 1-(2-chloro-7-fluoro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)piperazine | C18H18ClFN2S | 详情 | 详情 | |
| (C) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XI)The title compound was synthesized by two related procedures. 3-Fluoro-N-methylaniline (XIV) was obtained from 3-fluoroaniline (XI) by condensation with 1-(hydroxymethyl)benzotriazole (XII), followed by reduction of the anilinomethylbenzotriazole (XIII) with NaBH4. Subsequent condensation with 3-formylbenzoyl chloride (XV) (prepared from the corresponding acid and SOCl2) provided amide (XVI). Then, condensation of (XVI) with piperazine (V) and benzotriazole in the presence of a catalytic amount of Et3N in refluxing toluene furnished (XVII) as a mixture of epimers. 3-Bromophenol (XVIII) was protected as the silyl ether (XIX) with tert-butyldimethylsilyl chloride and imidazole. This compound was converted to the organolithium derivative with n-butyllithium in THF at -78 C, and further transformed to the arylmagnesium reagent (XX) by treatment with magnesium bromide etherate in THF. Condensation of (XVII) with organometallic compound (XX) afforded the benzhydrylpiperazine (XXI) as a 10:1 mixture of epimers. Desilylation of (XXI) by treatment with HCl in aqueous THF, followed by recrystallization of the major isomer from EtOAc/hexane yielded the title compound.
| 【1】 Chang, K.; Boswell, G.E.; Bubacz, D.G.; Collins, M.A.; Davis, A.O.; McNutt, R.W. (Delta Pharmaceuticals, Inc.); Opioid diarylmethylpiperazines and piperidines. JP 1995503247; US 5658908; US 5681830; WO 9315062 . |
| 【2】 Chang, K.-J.; Bishop, M.J.; Bubacz, D.G.; McNutt, R.W. Jr. (Glaxo Wellcome plc); Piperazine cpds. used in therapy. EP 0711289; JP 1997501156; WO 9504051 . |
| 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) | 20690 | (2R,5S)-1-allyl-2,5-dimethylpiperazine | C9H18N2 | 详情 | 详情 | |
| (XI) | 20697 | 3-fluoroaniline; 3-fluorophenylamine | 372-19-0 | C6H6FN | 详情 | 详情 |
| (XII) | 20698 | 1H-1,2,3-benzotriazol-1-ylmethanol | 28539-02-8 | C7H7N3O | 详情 | 详情 |
| (XIII) | 20699 | N-(1H-1,2,3-benzotriazol-1-ylmethyl)-3-fluoroaniline; N-(1H-1,2,3-benzotriazol-1-ylmethyl)-N-(3-fluorophenyl)amine | C13H11FN4 | 详情 | 详情 | |
| (XIV) | 20700 | 3-fluoro-N-methylaniline; N-(3-fluorophenyl)-N-methylamine | C7H8FN | 详情 | 详情 | |
| (XV) | 20701 | 3-formylbenzoyl chloride | C8H5ClO2 | 详情 | 详情 | |
| (XVI) | 20702 | N-(3-fluorophenyl)-3-formyl-N-methylbenzamide | C15H12FNO2 | 详情 | 详情 | |
| (XVII) | 20703 | 3-[[(2S,5R)-4-allyl-2,5-dimethylpiperazinyl](1H-1,2,3-benzotriazol-1-yl)methyl]-N-(3-fluorophenyl)-N-methylbenzamide | C30H33FN6O | 详情 | 详情 | |
| (XVIII) | 20704 | 3-bromophenol | 591-20-8 | C6H5BrO | 详情 | 详情 |
| (XIX) | 20705 | (3-bromophenoxy)(tert-butyl)dimethylsilane; 3-bromophenyl tert-butyl(dimethyl)silyl ether | 65423-56-5 | C12H19BrOSi | 详情 | 详情 |
| (XX) | 20706 | bromo(3-[[tert-butyl(dimethyl)silyl]oxy]phenyl)magnesium | C12H19BrMgOSi | 详情 | 详情 | |
| (XXI) | 20707 | 3-[[(2S,5R)-4-allyl-2,5-dimethylpiperazinyl](3-[[tert-butyl(dimethyl)silyl]oxy]phenyl)methyl]-N-(3-fluorophenyl)-N-methylbenzamide | C36H48FN3O2Si | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Reaction of 3-fluoroaniline (I) with formic acid gave formanilide (II), which was reduced by means of LiAlH4 to afford 3-fluoro-N-methylaniline (III). Further alkylation of (III) with benzyl chloride provided the tertiary amine (IV). Vilsmeier-Haack formylation of (IV) with POCl3 and DMF yielded aldehyde (V), which was condensed with nitroethane in the presence of ammonium acetate to give the 2-nitropropene derivative (VI). After reduction of (VI) to the amine (VII) with LiAlH4, condensation with chloroacetyl chloride afforded chloracetamide (VIII). Subsequent displacement of the chlorine of (VIII) with dibenzylamine yielded the tertiary amine (IX). Finally, hydrogenolytic debenzylation of (IX) in the presence of Pd/C furnished the title compound.
| 【1】 Larsson, L.-G.; Florvall, L.; Ross, S.B.; Fagervall, I.; Prodrugs of neuron-selective monoamine oxidase inhibitors: Amino acid derivatives of 1-(4-aminophenyl)-2-aminopropanes. Eur J Med Chem 1999, 34, 2, 137. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 | |
| 12117 | Nitroethane; 1-Nitroethane | 79-24-3 | C2H5NO2 | 详情 | 详情 | |
| 19171 | 1-(Chloromethyl)benzene; Benzyl chloride | 100-44-7 | C7H7Cl | 详情 | 详情 | |
| (I) | 20697 | 3-fluoroaniline; 3-fluorophenylamine | 372-19-0 | C6H6FN | 详情 | 详情 |
| (II) | 29575 | 3-fluorophenylformamide | C7H6FNO | 详情 | 详情 | |
| (III) | 20700 | 3-fluoro-N-methylaniline; N-(3-fluorophenyl)-N-methylamine | C7H8FN | 详情 | 详情 | |
| (IV) | 29576 | N-benzyl-3-fluoro-N-methylaniline; N-benzyl-N-(3-fluorophenyl)-N-methylamine | C14H14FN | 详情 | 详情 | |
| (V) | 29577 | 4-[benzyl(methyl)amino]-2-fluorobenzaldehyde | C15H14FNO | 详情 | 详情 | |
| (VI) | 29578 | N-benzyl-N-[3-fluoro-4-[(E)-2-nitro-1-propenyl]phenyl]-N-methylamine; N-benzyl-3-fluoro-N-methyl-4-[(E)-2-nitro-1-propenyl]aniline | C17H17FN2O2 | 详情 | 详情 | |
| (VII) | 29579 | N-[4-(2-aminopropyl)-3-fluorophenyl]-N-benzyl-N-methylamine; 4-(2-aminopropyl)-N-benzyl-3-fluoro-N-methylaniline | C17H21FN2 | 详情 | 详情 | |
| (VIII) | 29580 | N-(2-[4-[benzyl(methyl)amino]-2-fluorophenyl]-1-methylethyl)-2-chloroacetamide | C19H22ClFN2O | 详情 | 详情 | |
| (IX) | 29581 | N-(2-[4-[benzyl(methyl)amino]-2-fluorophenyl]-1-methylethyl)-2-(dibenzylamino)acetamide | C33H36FN3O | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)The reaction of 3-fluoroaniline (I) with isobutyl chloroformate (II) by means of K2CO3 in dichloromethane/water gives the carbamate (III), which is brominated with 1,3-dibromo-5,5-dimethylhydantoin (DBDH) to yield the 4-bromo-3-fluorophenyl carbamate (IV). The condensation of (IV) with tetrahydrothiopyran-4-one (V) by means of EtMgBr and BuLi in THF affords the tertiary alcohol (VI), which is dehydrated by means of TFA in dichloromethane and oxidized with NaIO4 in methanol/water to provide the unsaturated sulfoxide (VII). The stereoselective reduction of (VII) by means of H2 over Pt/C in DMF gives the cis sulfoxide (VIII). The cyclization of the carbamate (VIII) with (S)-3-chloropropane-1,2-diol (IX) by means of Li t-amylate in DMF gives the oxazolidinone (X), whose free OH group is activated with 2,5-dichlorobenzenesulfonyl chloride (XI) and TEA in dichloromethane to yield the sulfonate (XII). The reaction of (XII) with NH4OH in methanol/acetonitrile affords the aminomethyl derivative (XIII), which is finally acylated with acetic anhydride (XIV) to provide the target sulfoxide.
| 【1】 Gage, J.R.; et al.; Stereodivergent synthesis of sulfoxide-containing oxazolidinone antibiotics. Tetrahedron Lett 2000, 41, 22, 4301. |
| 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) | 20697 | 3-fluoroaniline; 3-fluorophenylamine | 372-19-0 | C6H6FN | 详情 | 详情 |
| (II) | 13423 | 1-[(Chlorocarbonyl)oxy]-2-methylpropane; Isobutyl chloroformate;isobutyl carbonochloridate | 543-27-1 | C5H9ClO2 | 详情 | 详情 |
| (III) | 49690 | isobutyl 3-fluorophenylcarbamate | C11H14FNO2 | 详情 | 详情 | |
| (IV) | 49691 | isobutyl 4-bromo-3-fluorophenylcarbamate | C11H13BrFNO2 | 详情 | 详情 | |
| (V) | 49692 | Tetrahydrothiopyran-4-one; Tetrahydro-4H-thiopyran-4-one; 4-Oxothiane | 1072-72-6 | C5H8OS | 详情 | 详情 |
| (VI) | 49693 | isobutyl 3-fluoro-4-(4-hydroxytetrahydro-2H-thiopyran-4-yl)phenylcarbamate | C16H22FNO3S | 详情 | 详情 | |
| (VII) | 49694 | 4-[2-fluoro-4-[(isobutoxycarbonyl)amino]phenyl]-3,6-dihydro-2H-thiopyranium-1-olate | C16H20FNO3S | 详情 | 详情 | |
| (VIII) | 49695 | 4-[2-fluoro-4-[(isobutoxycarbonyl)amino]phenyl]tetrahydro-2H-thiopyranium-1-olate | C16H22FNO3S | 详情 | 详情 | |
| (IX) | 49696 | (S)-(+)-Alpha-Chlorohydrin; (S)-(+)-3-Chloro-1,2-propanediol; (S)-3-Chloro-1,2-propanediol | 60827-45-4 | C3H7ClO2 | 详情 | 详情 |
| (X) | 49697 | 4-[2-fluoro-4-[(5R)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]tetrahydro-2H-thiopyranium-1-olate | C15H18FNO4S | 详情 | 详情 | |
| (XI) | 49698 | 2,5-Dichlorobenzenesulfonic acid | 88-42-6 | C6H4Cl2O3S | 详情 | 详情 |
| (XII) | 49699 | 4-[4-[(5R)-5-([[(2,5-dichlorophenyl)sulfonyl]oxy]methyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]tetrahydro-2H-thiopyranium-1-olate | C21H20Cl2FNO6S2 | 详情 | 详情 | |
| (XIII) | 49700 | 4-[4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]tetrahydro-2H-thiopyranium-1-olate | C15H19FN2O3S | 详情 | 详情 | |
| (XIV) | 49701 | Acetic anhydride; Acetyl oxide | 108-24-7 | C4H6O3 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(I)The reaction of 3-fluoroaniline (I) with isobutyl chloroformate (II) by means of K2CO3 in dichloromethane/water gives the carbamate (III), which is brominated with 1,3-dibromo-5,5-dimethylhydantoin (DBDH) to yield the 4-bromo-3-fluorophenyl carbamate (IV). The condensation of (IV) with tetrahydrothiopyran-4-one (V) by means of EtMgBr and BuLi in THF affords the tertiary alcohol (VI), which is dehydroxylated by means of poly(methylhydrosiloxane) (PMHS), (Me3Si)2O and Ts-OH in toluene to provide the intermediate (VII). The stereoselective oxidation of (VII) to the trans sulfoxide (VIII) is performed by means of Ti(OiPr)4 and tert-butyl hydroperoxide in the presence of diisopropyl D-tartrate. The cyclization of the carbamate (VIII) with (S)-3-chloropropane-1,2-diol (IX) by means of Li t-amylate in DMF gives the oxazolidinone (X), whose free OH group is activated with 3-nitrobenzenesulfonyl chloride and TEA in dichloromethane to yield the sulfonate (XII). The reaction of (XII) with NH4OH in methanol/acetonitrile affords the aminomethyl derivative (XIII), which is finally acylated with propionic anhydride (XIV) to provide the target sulfoxide.
| 【1】 Gage, J.R.; et al.; Stereodivergent synthesis of sulfoxide-containing oxazolidinone antibiotics. Tetrahedron Lett 2000, 41, 22, 4301. |
| 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) | 20697 | 3-fluoroaniline; 3-fluorophenylamine | 372-19-0 | C6H6FN | 详情 | 详情 |
| (II) | 13423 | 1-[(Chlorocarbonyl)oxy]-2-methylpropane; Isobutyl chloroformate;isobutyl carbonochloridate | 543-27-1 | C5H9ClO2 | 详情 | 详情 |
| (III) | 49690 | isobutyl 3-fluorophenylcarbamate | C11H14FNO2 | 详情 | 详情 | |
| (IV) | 49691 | isobutyl 4-bromo-3-fluorophenylcarbamate | C11H13BrFNO2 | 详情 | 详情 | |
| (V) | 49692 | Tetrahydrothiopyran-4-one; Tetrahydro-4H-thiopyran-4-one; 4-Oxothiane | 1072-72-6 | C5H8OS | 详情 | 详情 |
| (VI) | 49693 | isobutyl 3-fluoro-4-(4-hydroxytetrahydro-2H-thiopyran-4-yl)phenylcarbamate | C16H22FNO3S | 详情 | 详情 | |
| (VII) | 49702 | isobutyl 3-fluoro-4-tetrahydro-2H-thiopyran-4-ylphenylcarbamate | C16H22FNO2S | 详情 | 详情 | |
| (VIII) | 49706 | 4-[2-fluoro-4-[(isobutoxycarbonyl)amino]phenyl]tetrahydro-2H-thiopyranium-1-olate | C16H22FNO3S | 详情 | 详情 | |
| (IX) | 49696 | (S)-(+)-Alpha-Chlorohydrin; (S)-(+)-3-Chloro-1,2-propanediol; (S)-3-Chloro-1,2-propanediol | 60827-45-4 | C3H7ClO2 | 详情 | 详情 |
| (X) | 49707 | 4-[2-fluoro-4-[(5R)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]tetrahydro-2H-thiopyranium-1-olate | C15H18FNO4S | 详情 | 详情 | |
| (XI) | 49703 | m-nitrobenzenesulfonic acid; 3-nitrobenzenesulfonic acid | 98-47-5 | C6H5NO5S | 详情 | 详情 |
| (XII) | 49704 | 4-[2-fluoro-4-[(5R)-5-([[(3-nitrophenyl)sulfonyl]oxy]methyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]tetrahydro-2H-thiopyranium-1-olate | C21H21FN2O8S2 | 详情 | 详情 | |
| (XIII) | 49705 | 4-[4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]tetrahydro-2H-thiopyranium-1-olate | C15H19FN2O3S | 详情 | 详情 | |
| (XIV) | 49701 | Acetic anhydride; Acetyl oxide | 108-24-7 | C4H6O3 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(I)Condensation of 3-fluoroaniline (I) with the cyclic anhydride (II) in AcOH gave amide (III). Subsequent cyclization of (III) in hot H2SO4 produced quinolineacetic acid (IV). After esterification of (IV) with methanol in the presence of SOCl2, the resulting methyl ester (V) was reduced to alcohol (VI) using NaBH4 in refluxing THF. Treatment of alcohol (VI) with SOCl2 afforded chloride (VII), which was condensed with 4-(1-piperazinyl)thieno[3,2-c]pyridine (VIII) yielding adduct (IX), isolated as the dihydro-chloride salt. Finally, alkylation of the quinoline N atom of (IX) with bromoacetamide (A) under phase-transfer conditions furnished the title compound.
| 【1】 McCort, G.; et al.; Synthesis and SAR of 3- and 4-substituted quinolin-2-ones: Discovery of mixed 5-HT1b/5-HT2A receptor antagonists. Bioorg Med Chem 2001, 9, 8, 2129. |
| 【2】 Demarquay, D.; Lavergne, O.; Bailly, C.; et al.; Topoisomerase I-mediated antiproliferative activity of enantiomerically pure fluorinated homocamptothecins. J Med Chem 2000, 43, 11, 2285. |
| 【3】 Mc Cort, G.; Hoornaert, C.; Dellac, G.; Aletru, M. (Sanofi-Synthelabo ); Quinolein-2(1H)-one derivs. as serotonin antagonists. EP 0850235; FR 2738822; FR 2739100; JP 1999514982; US 5958924; WO 9710238 . |
| 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) | 38747 | 2-bromoacetamide | 683-57-8 | C2H4BrNO | 详情 | 详情 |
| (I) | 20697 | 3-fluoroaniline; 3-fluorophenylamine | 372-19-0 | C6H6FN | 详情 | 详情 |
| (II) | 40692 | 2,6-dioxo-3,6-dihydro-2H-pyran-4-yl acetate | C7H6O5 | 详情 | 详情 | |
| (III) | 40693 | (Z)-3-(acetoxy)-5-(3-fluoroanilino)-5-oxo-2-pentenoic acid | C13H12FNO5 | 详情 | 详情 | |
| (IV) | 40694 | 2-(7-fluoro-2-oxo-1,2-dihydro-4-quinolinyl)acetic acid | C11H8FNO3 | 详情 | 详情 | |
| (V) | 40695 | methyl 2-(7-fluoro-2-oxo-1,2-dihydro-4-quinolinyl)acetate | C12H10FNO3 | 详情 | 详情 | |
| (VI) | 40696 | 7-fluoro-4-(2-hydroxyethyl)-2(1H)-quinolinone | C11H10FNO2 | 详情 | 详情 | |
| (VII) | 40697 | 4-(2-chloroethyl)-7-fluoro-2(1H)-quinolinone | C11H9ClFNO | 详情 | 详情 | |
| (VIII) | 40698 | 4-(1-piperazinyl)thieno[3,2-c]pyridine | C11H13N3S | 详情 | 详情 | |
| (IX) | 40699 | 7-fluoro-4-[2-(4-thieno[3,2-c]pyridin-4-yl-1-piperazinyl)ethyl]-2(1H)-quinolinone | C22H21FN4OS | 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 alkylation of 3-fluoroaniline (I) with 2-bromoacetamide (II) by means of KOH and Bu4NBr in THF gives 2-(3-fluorophenylamino)acetamide (III), which is condensed with 4-acetoxy-3,6-dihydro-2H-pyran-2,6-dione (IV) in Ac-OH to yield intermediate (V). The cyclization of (V) by means of H2SO4 or Ms-OH at 100?C affords the quinolone (VII), which is esterified with SOCl2 and methanol to provide the corresponding methyl ester (VII). The reduction of (VII) with NaBH4 in refluxing THF furnishes the 2-hydroxyethyl quinolone (VIII), which is treated with SOCl2 in refluxing CHCl3 to give the 2-chloroethyl derivative (IX). Finally, this compound is condensed with the arylpiperazine (X) by means of K2CO3 and KI in hot DMF to afford the desired quinolone.
| 【1】 McCort, G.; et al.; Synthesis and SAR of 3- and 4-substituted quinolin-2-ones: Discovery of mixed 5-HT1b/5-HT2A receptor antagonists. Bioorg Med Chem 2001, 9, 8, 2129. |
| 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) | 20697 | 3-fluoroaniline; 3-fluorophenylamine | 372-19-0 | C6H6FN | 详情 | 详情 |
| (II) | 38747 | 2-bromoacetamide | 683-57-8 | C2H4BrNO | 详情 | 详情 |
| (III) | 50951 | 2-(3-fluoroanilino)acetamide | C8H9FN2O | 详情 | 详情 | |
| (IV) | 40692 | 2,6-dioxo-3,6-dihydro-2H-pyran-4-yl acetate | C7H6O5 | 详情 | 详情 | |
| (V) | 50952 | (Z)-3-(acetoxy)-5-[(2-amino-2-oxoethyl)-3-fluoroanilino]-5-oxo-2-pentenoic acid | C15H15FN2O6 | 详情 | 详情 | |
| (VI) | 50953 | 2-[1-(2-amino-2-oxoethyl)-7-fluoro-2-oxo-1,2-dihydro-4-quinolinyl]acetic acid | C13H11FN2O4 | 详情 | 详情 | |
| (VII) | 50954 | methyl 2-[1-(2-amino-2-oxoethyl)-7-fluoro-2-oxo-1,2-dihydro-4-quinolinyl]acetate | C14H13FN2O4 | 详情 | 详情 | |
| (VIII) | 50955 | 2-[7-fluoro-4-(2-hydroxyethyl)-2-oxo-1(2H)-quinolinyl]acetamide | C13H13FN2O3 | 详情 | 详情 | |
| (IX) | 50956 | 2-[4-(2-chloroethyl)-7-fluoro-2-oxo-1(2H)-quinolinyl]acetamide | C13H12ClFN2O2 | 详情 | 详情 | |
| (X) | 40698 | 4-(1-piperazinyl)thieno[3,2-c]pyridine | C11H13N3S | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(I)Synthesis of intermediate (VII): Conversion of 3-fluoroaniline (I) into 2-amino-5-fluorobenzothiazole (III) can be achieved by first coupling with isocyanate (II) followed by hydrolysis with NaOH, reaction with Br2 and finally heating treatment. Dimerization of substituted benzothiazole (III) by means of refluxing aqueous KOH yields disulfide derivative (IV), which is then condensed with substituted benzoyl chloride (V) in refluxing pyridine to afford derivative (VI). Finally, (VI) is converted into intermediate (VII) by treatment with SnCl2 dihydrate in refluxing HCl/EtOH. Alternatively, intermediate (VII) can be synthesized as follows: substituted aniline (VIII) is first brominated via a Sandmeyer reaction with NaNO2 in HBr and CuBr, and then the nitro group is reduced with SnCl2 in refluxing EtOH to provide derivative (IX). Condensation of (IX) with substituted benzoyl chloride (V) in refluxing pyridine yields amide (X), which is then first treated with Lawesson's reagent and HMPA and then with NaH in NMP to afford benzothiazole derivative (XI). Finally, the nitro group of (XI) is reduced with SnCl2 in refluxing EtOH to yield intermediate (VII). Synthesis of EN 295753: The desired compound can finally be obtained by coupling of intermediate (VII) with Boc-Lys(Boc)-OH (XII) by means of carbodiimide WSC.HCl and HOBt in CH2Cl2, followed by Boc removal with HCl (gas) in CH2Cl2.
| 【1】 Hutchinson, I.; et al.; Antitumor benzothiazoles. 16. Synthesis and pharmaceutical properties of antitumor 2-(4-aminophenyl)benzothiazole amino acid produgs. J Med Chem 2002, 45, 3, 744. |
| 【2】 Chua, M.-S.; Westwell, A.D.; Hutchinson, I.P.; Stevens, M.F.G.; Poole, T.D. (Cancer Research Campaign Technology Ltd.); Substd. 2-arylbenzazole cpds. and their use as antitumour agents. WO 0114354 . |
| 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) | 20697 | 3-fluoroaniline; 3-fluorophenylamine | 372-19-0 | C6H6FN | 详情 | 详情 |
| (II) | 23530 | benzoyl isothiocyanate | 532-55-8 | C8H5NOS | 详情 | 详情 |
| (III) | 47594 | 5-fluoro-1,3-benzothiazol-2-amine; 5-fluoro-1,3-benzothiazol-2-ylamine | C7H5FN2S | 详情 | 详情 | |
| (IV) | 47595 | 2-[(2-amino-4-fluorophenyl)disulfanyl]-5-fluoroaniline; 2-[(2-amino-4-fluorophenyl)disulfanyl]-5-fluorophenylamine | C12H10F2N2S2 | 详情 | 详情 | |
| (V) | 47596 | 3-methyl-4-nitrobenzoyl chloride | 35675-46-8 | C8H6ClNO3 | 详情 | 详情 |
| (VI) | 47597 | N-[5-fluoro-2-([4-fluoro-2-[(3-methyl-4-nitrobenzoyl)amino]phenyl]disulfanyl)phenyl]-3-methyl-4-nitrobenzamide | C28H20F2N4O6S2 | 详情 | 详情 | |
| (VII) | 47598 | 1-(5-fluoro-1,3-benzothiazol-2-yl)-3-methyl-1lambda(5)-pyridin-4-amine; 1-(5-fluoro-1,3-benzothiazol-2-yl)-3-methyl-1lambda(5)-pyridin-4-ylamine | C13H12FN3S | 详情 | 详情 | |
| (VIII) | 22288 | 4-fluoro-2-nitrophenylamine; 4-fluoro-2-nitroaniline | 364-78-3 | C6H5FN2O2 | 详情 | 详情 |
| (IX) | 47599 | 2-bromo-5-fluoroaniline; 2-bromo-5-fluorophenylamine | 1003-99-2 | C6H5BrFN | 详情 | 详情 |
| (X) | 47600 | N-(2-bromo-5-fluorophenyl)-3-methyl-4-nitrobenzamide | C14H10BrFN2O3 | 详情 | 详情 | |
| (XI) | 47602 | methyl 3-(1-trityl-1H-imidazol-4-yl)propanoate | C26H24N2O2 | 详情 | 详情 | |
| (XII) | 37991 | (2S)-2,6-bis[(tert-butoxycarbonyl)amino]hexanoic acid | 2483-46-7 | C16H30N2O6 | 详情 | 详情 |
| (XIII) | 47601 | tert-butyl (1S)-5-[(tert-butoxycarbonyl)amino]-1-([[1-(5-fluoro-1,3-benzothiazol-2-yl)-3-methyl-1lambda(5)-pyridin-4-yl]amino]carbonyl)pentylcarbamate | C29H40FN5O5S | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(I)Addition of thiocyanogen (generated in situ from KSCN and N-bromosuccinimide) to 3-fluoroaniline (I) gave the thiocyanoaniline (II). Subsequent acylation of aniline (II) with benzyl chloroformate afforded carbamate (III). The intermediate thiol produced by treatment of thiocyanate (III) with sodium sulfide was captured as the trityl sulfide (IV) upon quenching with bromotriphenylmethane. The chiral oxazolidinone (VI) was then obtained by condensation of the lithium salt of carbamate (IV) with (R)-glycidyl butyrate (V). Activation of the primary hydroxyl of (VI) as the corresponding mesylate (VII), followed by displacement with NaN3 in hot DMF gave rise to the alkyl azide (VIII). Removal of the S-trityl protecting group of (VIII) by means of trifluoroacetic acid and triisopropylsilane and further alkylation of the resultant thiol with iodomethane yielded the methyl sulfide (IX). Sulfoxide (X) was then obtained by oxidation of sulfide (IX) with m-chloroperbenzoic acid. Reduction of the azido group of (X) to the required amine (XI) was accomplished by treatment with triphenylphosphine followed by aqueous hydrolysis. Finally, condensation of amine (XI) with ethyl dithioacetate furnished the title thioacetamide.
| 【1】 Gadwood, R.C.; Patel, D.V.; Hackbarth, C.J.; Gordeev, M.F.; Luehr, G.W.; Lopez, S.; Trias, J.; Acyclic C-group oxazolidinones: Antimicrobial activity of novel 4'-Sulfide and 4'-sulfoxide 3'-fluorophenyl oxazolidinones. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1044. |
| 【2】 Patel, D.V.; Gadwood, R.C.; Gordeev, M.F.; Luehr, G.W. (Pharmacia Corp.); Oxazolidinones and their use as antiinfectives. EP 1200416; US 6441005; WO 0109107 . |
| 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) | 20697 | 3-fluoroaniline; 3-fluorophenylamine | 372-19-0 | C6H6FN | 详情 | 详情 |
| (II) | 56095 | 4-amino-2-fluorobenzenesulfenyl cyanide | C7H5FN2S | 详情 | 详情 | |
| (III) | 56096 | benzyl 4-(cyanosulfanyl)-3-fluorophenylcarbamate | C15H11FN2O2S | 详情 | 详情 | |
| (IV) | 56097 | benzyl 3-fluoro-4-(tritylsulfanyl)phenylcarbamate | C33H26FNO2S | 详情 | 详情 | |
| (V) | 18385 | (2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate | 60456-26-0 | C7H12O3 | 详情 | 详情 |
| (VI) | 56098 | (5R)-3-[3-fluoro-4-(tritylsulfanyl)phenyl]-5-(hydroxymethyl)-1,3-oxazolidin-2-one | C29H24FNO3S | 详情 | 详情 | |
| (VII) | 56099 | {(5R)-3-[3-fluoro-4-(tritylsulfanyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl methanesulfonate | C30H26FNO5S2 | 详情 | 详情 | |
| (VIII) | 56100 | (5R)-5-(azidomethyl)-3-[3-fluoro-4-(tritylsulfanyl)phenyl]-1,3-oxazolidin-2-one | C29H23FN4O2S | 详情 | 详情 | |
| (IX) | 56101 | (5R)-5-(azidomethyl)-3-[3-fluoro-4-(methylsulfanyl)phenyl]-1,3-oxazolidin-2-one | C11H11FN4O2S | 详情 | 详情 | |
| (X) | 56102 | (5R)-5-(azidomethyl)-3-[3-fluoro-4-(methylsulfinyl)phenyl]-1,3-oxazolidin-2-one | C11H11FN4O3S | 详情 | 详情 | |
| (XI) | 56103 | (5S)-5-(aminomethyl)-3-[3-fluoro-4-(methylsulfinyl)phenyl]-1,3-oxazolidin-2-one | C11H13FN2O3S | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(I)The condensation of 3-fluoroaniline (I) with 4-fluorobenzonitrile (II) by means of BCl3 and AlCl3 in xylene at 120 C gives the benzophenone (III), which is reduced with hydrazine and KOH in ethyleneglycol at 200 C to yield the diphenylmethane (IV). The acylation of the NH2 group of (IV) with refluxing formic acid affords the formamide (V), which is cyclized by means of PPA and POCl3 in xylene at 100 C to provide the dibenzazepine (VI). The reduction of (VI) with H2 over Pd/C in THF/methanol gives the corresponding dihydro compound (VII), which is oxidized with 3-phenyl-2-(phenylsulfonyl)oxaziridine (VIII) in dichloromethane to yield the N-oxide (IX). Finally, this compound is cyclized with N-allyl-N,N-dimethylamine (X) by heating in toluene at 100 C to afford the target oxazolidine derivative. Alternatively, the cyclization of 5-fluoro-2-hydroxyaniline (XI) with 3-fluorobenzaldehyde (XII) by means of chloroacetic acid at 100 C in methanol or isopropanol gives 7-fluoro-2-(4-fluorophenyl)-2,4-dihydro-1H-3,1-benzoxazine (XIII), which is reduced with NaBH4 in refluxing ethanol to yield N-(3-fluorobenzyl)-N-[2-(hydroxymethyl)-5-fluorophenyl]amine (XIV). Finally, this compound is cyclized by means of H2SO4 in dichloromethane to afford the previously described dihydro-benzodiazepine (VII), which is worked up as before.
| 【1】 Alonso, J.M.; Alcázar, J.; Andrés, J.I.; et al.; Synthesis and structure-activity relationship of 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives: A novel series of 5-HT2A/2C receptor antagonists. Part 2. Bioorg Med Chem Lett 2002, 12, 2, 249. |
| 【2】 Sipido, V.K.; Fernandez-Gadea, F.J.; Andres-Gil, J.I.; Meert, T.F.; Gil-Lopetegui, P. (Janssen Pharmaceutica NV); Substd. tetracyclic azepine derivs. which have affinity for 5-HT2 receptors. EP 0789701; JP 1998508308; US 5552399; WO 9614320 . |
| 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) | 20697 | 3-fluoroaniline; 3-fluorophenylamine | 372-19-0 | C6H6FN | 详情 | 详情 |
| (II) | 14144 | 4-Fluorobenzonitrile | 1194-02-1 | C7H4FN | 详情 | 详情 |
| (III) | 54726 | (2-amino-4-fluorophenyl)(4-fluorophenyl)methanone | C13H9F2NO | 详情 | 详情 | |
| (IV) | 54727 | 5-fluoro-2-(4-fluorobenzyl)aniline; 5-fluoro-2-(4-fluorobenzyl)phenylamine | C13H11F2N | 详情 | 详情 | |
| (V) | 54728 | 5-fluoro-2-(4-fluorobenzyl)phenylformamide | C14H11F2NO | 详情 | 详情 | |
| (VI) | 54729 | 3,8-difluoro-11H-dibenzo[b,e]azepine | C14H9F2N | 详情 | 详情 | |
| (VII) | 54730 | 3,8-difluoro-6,11-dihydro-5H-dibenzo[b,e]azepine | C14H11F2N | 详情 | 详情 | |
| (VIII) | 31834 | 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine;2-(Phenylsulfonyl)-3-phenyloxaziridine;2-Benzenesulfonyl-3-phenyloxaziridine;3-Phenyl-2-phenylsulfonyloxaziridine;3-Phenyl-N-phenylsulfonyloxaziridine;N-(Phenylsulfonyl)phenyloxaziridine;N-Benzenesulfonyl-3-phenyloxaziridine | 63160-13-4 | C13H11NO3S | 详情 | 详情 |
| (IX) | 54731 | 3,8-difluoro-11H-dibenzo[b,e]azepinium-5-olate | C14H9F2NO | 详情 | 详情 | |
| (X) | 54732 | 1-Dimethylamino-2-propene; Allyldimethylamine; N,N-Dimethylallylamine; N-Allyl-N,N-dimethylamine | 2155-94-4 | C5H11N | 详情 | 详情 |
| (XI) | 54733 | 2-amino-4-fluorophenol | C6H6FNO | 详情 | 详情 | |
| (XII) | 18887 | 3-Fluorobenzaldehyde | 456-48-4 | C7H5FO | 详情 | 详情 |
| (XIII) | 54734 | 7-fluoro-2-(3-fluorophenyl)-1,4-dihydro-2H-3,1-benzoxazine | C14H11F2NO | 详情 | 详情 | |
| (XIV) | 54735 | {4-fluoro-2-[(3-fluorobenzyl)amino]phenyl}methanol | C14H13F2NO | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(I)Reaction of 3-fluoroaniline (I) with benzyl chloroformate provides carbamate (II). The lithium derivative of (II) is then condensed with (R)-glycidyl butyrate (III) to yield the chiral oxazolidinone (IV). After conversion of alcohol (IV) to the corresponding mesylate (V), displacement with NaN3 in hot DMF gives rise to the alkyl azide (VI). Catalytic hydrogenation of azide (VI) furnishes amine (VII), which is further acylated with acetic anhydride, producing acetamide (VIII). Aromatic iodination of (VIII) by means of iodine monochloride in the presence of trifluoroacetic acid gives (IX). Iodide compound (IX) is then converted into the aryl stannane (X) upon treatment with hexamethyl ditin and palladium catalyst
| 【1】 Im, W.; Lee, T.; Cho, J.; Choi, S.; Rhee, J.; In vitro and in vivo studies of hetero-ring substituted pyridine containing oxazolidinone derivatives, including DA-7867. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1311. |
| 【2】 Lee, J.-G.; Lee, J.-J.; Park, S.-K.; Lee, T.-H.; Leem, W.-B.; Cho, J.-H.; Choi, S.-H.; Kim, D.-G.; Sung, H.-J. (Dong-A Pharmaceutical Co., Ltd.); Novel oxazolidinone derivs. and a process for the preparation thereof. WO 0194342 . |
| 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) | 20697 | 3-fluoroaniline; 3-fluorophenylamine | 372-19-0 | C6H6FN | 详情 | 详情 |
| (II) | 60314 | phenylmethyl 3-fluorophenylcarbamate | C14H12FNO2 | 详情 | 详情 | |
| (III) | 18385 | (2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate | 60456-26-0 | C7H12O3 | 详情 | 详情 |
| (IV) | 60315 | 3-(3-fluorophenyl)-5-(hydroxymethyl)-1,3-oxazolidin-2-one | C10H10FNO3 | 详情 | 详情 | |
| (V) | 60316 | [3-(3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl methanesulfonate | C11H12FNO5S | 详情 | 详情 | |
| (VI) | 60317 | (R)-5-(azidomethyl)-3-(3-fluorophenyl)oxazolidin-2-one | C10H9FN4O2 | 详情 | 详情 | |
| (VII) | 60318 | 5-(aminomethyl)-3-(3-fluorophenyl)-1,3-oxazolidin-2-one | C10H11FN2O2 | 详情 | 详情 | |
| (VIII) | 60319 | N-{[3-(3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide | C12H13FN2O3 | 详情 | 详情 | |
| (IX) | 38138 | N-[[(5S)-3-(3-fluoro-4-iodophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide | C12H12FIN2O3 | 详情 | 详情 | |
| (X) | 60320 | N-({3-[3-fluoro-4-(trimethylstannanyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide | C15H21FN2O3Sn | 详情 | 详情 |
合成路线12
该中间体在本合成路线中的序号：(I)3-Fluoroaniline (I) is condensed with benzyl chloroformate to give carbamate (II). Reaction of (II) with (R)-glycidol butyrate (III) in the presence of butyllithium affords oxazolidinone (IV). After conversion of alcohol (IV) to the corresponding mesylate, displacement with NaN3 provides azide (V). Reduction and acylation of (V) by means of thioacetic acid leads to acetamide (VI). Friedel-Crafts acylation of the aromatic ring of (VI) with acetic anhydride in the presence of methanesulfonic acid furnishes acetophenone (VII). Acidic hydrolysis of acetamide (VII) yields amine (VIII). This is then treated with thiophosgene, followed by methanol, to produce the thiocarbamate (IX). Finally, aldol condensation of the acetophenone (IX) with pyridine-2-carbaldehyde (X) gives rise to the target compound.
| 【1】 Selvakumar, N.; et al.; Synthesis and antibacterial activity of novel chalcone oxazolidinone hybrids. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1323. |
| 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) | 20697 | 3-fluoroaniline; 3-fluorophenylamine | 372-19-0 | C6H6FN | 详情 | 详情 |
| (II) | 60314 | phenylmethyl 3-fluorophenylcarbamate | C14H12FNO2 | 详情 | 详情 | |
| (III) | 18385 | (2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate | 60456-26-0 | C7H12O3 | 详情 | 详情 |
| (IV) | 60315 | 3-(3-fluorophenyl)-5-(hydroxymethyl)-1,3-oxazolidin-2-one | C10H10FNO3 | 详情 | 详情 | |
| (V) | 60317 | (R)-5-(azidomethyl)-3-(3-fluorophenyl)oxazolidin-2-one | C10H9FN4O2 | 详情 | 详情 | |
| (VI) | 60319 | N-{[3-(3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide | C12H13FN2O3 | 详情 | 详情 | |
| (VII) | 62789 | N-{[(5S)-3-(4-acetyl-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide | C14H15FN2O4 | 详情 | 详情 | |
| (VIII) | 62790 | (5S)-3-(4-acetyl-3-fluorophenyl)-5-(aminomethyl)-1,3-oxazolidin-2-one | C12H13FN2O3 | 详情 | 详情 | |
| (IX) | 62791 | O-methyl [(5S)-3-(4-acetyl-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methylcarbamothioate | C14H15FN2O4S | 详情 | 详情 | |
| (X) | 25173 | 2-pyridinecarbaldehyde | 1121-60-4 | C6H5NO | 详情 | 详情 |