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【结 构 式】 
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【分子编号】17398 【品名】2-methoxyphenyl methyl ether; Veratrole; 1,2-dimethoxybenzene 【CA登记号】91-16-7 |
【 分 子 式 】C8H10O2 【 分 子 量 】138.1662 【元素组成】C 69.55% H 7.3% O 23.16% |
合成路线1
该中间体在本合成路线中的序号：(XXIX)Nitration of 1,2-dimethoxybenzene (XXIX) with HNO3/AcOH gives 4,5-dimethoxy-1,2-dinitrobenzene (XXX), which is treated with ammonia in hot methanol to yield 4,5-dimethoxy-2-nitroaniline (XXXI). Cyclization of compound (XXXI) with buten-2-one (XXXII) by means of H3PO4 and H3AsO4 affords 5,6-dimethoxy-4-methyl-8-nitroquinoline (XXXIII), which is selectively mono-demethylated by means of HCl in ethanol to provide 5-hydroxy-6-methoxy-4-methyl-8-nitroquinoline (XXXIV). Reaction of quinoline (XXXIV) with POCl3 gives the corresponding 5-chloro derivative (XXXV), which is condensed with 3-(trifluoromethyl)phenol (IV) by means of KOH to yield the diaryl ether (XXXVI). Finally, the nitro group of (XXXVI) is reduced by means of H2 over PtO2 in THF or H2 over Raney nickel.
| 【1】 McIntyre, J.A.; Castaner, J.; Bayes, M.; Tafenoquine Succinate. Drugs Fut 2003, 28, 9, 859. |
| 【2】 LaMontagne, M.P.; Blumbergs, P.; Strube, R.E.; Antimalarials. 14. 5-(Aryloxy)-4-methylprimaquine analogues. A highly effective series of blood and tissue schizonticidal agents. J Med Chem 1982, 25, 9, 1094. |
| 【3】 LaMontagne, M.P.; Strube, R.E. (Department of the Army); 4-Methyl-5-(unsubstd. and substd. phenoxy)-6-methoxy-8-(aminoalkylamino)quinolines. US 4431807 . |
| 【4】 LaMontagne, M.P.; et al.; Tricyclic compounds as selective muscarinic receptor antagonists. 3. Structure-selectivity relationships in a series of cardioselective (M2) antimuscarinics. J Med Chem 1989, 32, 8, 1728-32. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 33504 | 3-(trifluoromethyl)phenol | 98-17-9 | C7H5F3O | 详情 | 详情 |
| (XIV) | 48075 | 6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinylamine; 6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinamine | C18H15F3N2O2 | 详情 | 详情 | |
| (XXIX) | 17398 | 2-methoxyphenyl methyl ether; Veratrole; 1,2-dimethoxybenzene | 91-16-7 | C8H10O2 | 详情 | 详情 |
| (XXX) | 43039 | 2-methoxy-4,5-dinitrophenyl methyl ether; 1,2-dimethoxy-4,5-dinitrobenzene | 3395-03-7 | C8H8N2O6 | 详情 | 详情 |
| (XXXI) | 62902 | 4,5-dimethoxy-2-nitrophenylamine; 4,5-dimethoxy-2-nitroaniline | C8H10N2O4 | 详情 | 详情 | |
| (XXXII) | 30324 | 3-buten-2-one; methyl vinyl ketone | 78-94-4 | C4H6O | 详情 | 详情 |
| (XXXIII) | 62903 | 5,6-dimethoxy-4-methyl-8-nitroquinoline; 5-methoxy-4-methyl-8-nitro-6-quinolinyl methyl ether | C12H12N2O4 | 详情 | 详情 | |
| (XXXIV) | 62904 | 6-methoxy-4-methyl-8-nitro-5-quinolinol | C11H10N2O4 | 详情 | 详情 | |
| (XXXV) | 62905 | 5-Chloro-4-methyl-8-nitro-6-quinolinyl methyl ether; 5-Chloro-6-methoxy-4-methyl-8-nitroquinoline | C11H9ClN2O3 | 详情 | 详情 | |
| (XXXVI) | 62906 | 6-Methoxy-4-methyl-8-nitro-5-[3-(trifluoromethyl)phenoxy]quinoline; 6-Methoxy-4-methyl-8-nitro-5-quinolinyl 3-(trifluoromethyl)phenyl ether | C18H13F3N2O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)MDL-100907 can be obtained by several different ways: 1) The condensation of piperidine-4-carboxamide (I) with 2-(4-fluorophenyl)ethyl bromide (II) by means of K2CO3 in hot DMF gives 1-[2-(4-fluorophenyl)ethyl]piperidine-4-carboxamide (III), which by reaction with refluxing POCl3 is converted into the nitrile (IV). The reduction of (IV) with diisobutyl aluminum hydride (DIBAL) in THF affords the aldehyde (V), which by condensation with 1,2-dimethoxybenzene (veratrole) (VI) by means of BuLi in THF affords racemic MDL-100907 (VII). The esterification of (VII) with (S)-2-methoxy-2-phenylacetic acid (VIII) by means of dicyclohexylcarbodiimide (DCC) and dimethyl-aminopyridine (DMAP) in refluxing CHCl3 affords a mixture of diastereomers that is submitted to column chromatography over silica gel to afford the pure diastereomer (IX). Finally, (IX) is saponified with K2CO3 in methanol/ water
| 【1】 Castaner, J.; Sorbera, L.A.; Silvestre, J.S.; MDL-100907. Drugs Fut 1998, 23, 9, 955. |
| 【2】 Carr, A.A.; Kane, J.M.; Hay, D.A. (Merrell Pharmaceuticals, Inc.); (+)-*-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol. EP 0531410; JP 1993507482; US 5134149; WO 9118602 . |
| 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) | 11762 | 4-Piperidinecarboxamide; Isonipecotamide | 39546-32-2 | C6H12N2O | 详情 | 详情 |
| (II) | 17394 | 1-(2-bromoethyl)-4-fluorobenzene | C8H8BrF | 详情 | 详情 | |
| (III) | 17395 | 1-(4-fluorophenethyl)-4-piperidinecarboxamide | C14H19FN2O | 详情 | 详情 | |
| (IV) | 17396 | 1-(4-fluorophenethyl)-4-piperidinecarbonitrile | C14H17FN2 | 详情 | 详情 | |
| (V) | 17397 | 1-(4-fluorophenethyl)-4-piperidinecarbaldehyde | C14H18FNO | 详情 | 详情 | |
| (VI) | 17398 | 2-methoxyphenyl methyl ether; Veratrole; 1,2-dimethoxybenzene | 91-16-7 | C8H10O2 | 详情 | 详情 |
| (VII) | 17399 | (2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanol | C22H28FNO3 | 详情 | 详情 | |
| (VIII) | 17400 | (2S)-2-methoxy-2-phenylethanoic acid | C9H10O3 | 详情 | 详情 | |
| (IX) | 17401 | (R)-(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methyl (2S)-2-methoxy-2-phenylethanoate | C31H36FNO5 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VI)2) Racemic MDL-100907 (VII) can also be obtained by reaction of piperidine-4-carboxylic acid (X) with di-tert-butyl dicarbonate (XI) by means of NaOH in tert-butanol/ water, giving piperidine-1,4-dicarboxylic acid 1-mono-tert-butyl ester (XII), which is treated with N,O-dimethylhydroxylamine (XIII) and carbonyldiimidazole (CDI) in dichloromethane to afford the methoxy(methyl)amide (XIV). The condensation of (XIV) with veratrole (VI) by means of BuLi in THF gives 4-(2,3-dimethoxybenzoyl)-piperidine-1-carboxylic acid tert-butyl ester (XV), which is decarboxylated by means of trifluoroacetic acid, yielding ketone (XVI). The condensation of (XVI) with 2-(4-fluorophenyl)ethyl bromide (II) by means of K2CO3 in DMF affords 1-(2,3-dimethoxyphenyl)-1-[1-[2-(4-fluorophenyl)-ethyl]piperidin-4-yl]methanone (XVII). Finally, this compound is reduced with NaBH4 in methanol
| 【1】 Castaner, J.; Sorbera, L.A.; Silvestre, J.S.; MDL-100907. Drugs Fut 1998, 23, 9, 955. |
| 【2】 Carr, A.A.; Kane, J.M.; Hay, D.A. (Merrell Pharmaceuticals, Inc.); (+)-*-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol. EP 0531410; JP 1993507482; US 5134149; WO 9118602 . |
| 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) | 17394 | 1-(2-bromoethyl)-4-fluorobenzene | C8H8BrF | 详情 | 详情 | |
| (VI) | 17398 | 2-methoxyphenyl methyl ether; Veratrole; 1,2-dimethoxybenzene | 91-16-7 | C8H10O2 | 详情 | 详情 |
| (VII) | 17399 | (2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanol | C22H28FNO3 | 详情 | 详情 | |
| (X) | 17402 | 4-nipecotic acid;piperidine-4-carboxylic acid;p-nipecotic acid; Isonipecotic acid; Hexahydroisonicotinic acid; 4-Piperidinecarboxylic acid | 498-94-2 | C6H11NO2 | 详情 | 详情 |
| (XI) | 13214 | Di-tert-butyldicarbonate; Dicarbonic acid bis(1,1-dimethylethyl) ester; dicarbonic acid di-tert-butyl ester pyrocarbonic acid di-tert-butyl ester; bis(1,1-dimethylethyl) dicarbonate di-tert-butyl pyrocarbonate | 24424-99-5 | C10H18O5 | 详情 | 详情 |
| (XII) | 17404 | 1-(tert-butoxycarbonyl)-4-piperidinecarboxylic acid; 1-BOC-piperidine-4-carboxylic acid; N-Boc-isonipecotic acid | 84358-13-4 | C11H19NO4 | 详情 | 详情 |
| (XIII) | 13361 | (Methoxyamino)methane; N,O-Dimethylhydroxylamine | 1117-97-1 | C2H7NO | 详情 | 详情 |
| (XIV) | 17406 | tert-butyl 4-[[methoxy(methyl)amino]carbonyl]tetrahydro-1(2H)-pyridinecarboxylate | C13H24N2O4 | 详情 | 详情 | |
| (XV) | 17407 | tert-butyl 4-(2,3-dimethoxybenzoyl)tetrahydro-1(2H)-pyridinecarboxylate | C19H27NO5 | 详情 | 详情 | |
| (XVI) | 17408 | (2,3-dimethoxyphenyl)(4-piperidinyl)methanone | C14H19NO3 | 详情 | 详情 | |
| (XVII) | 17409 | (2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanone | C22H26FNO3 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(VI)3) Racemic MDL-100907 (VII) can also be obtained as follows: The reaction of piperidine-4-carboxylic acid ethyl ester (XVIII) with the previously mentioned bromide (II) by means of K2CO3 as before gives 1-[2-(4-fluorophenyl)ethyl]piperidine-4-carboxylic acid ethyl ester (XIX), which is treated with N,O-dimethylhydroxylamine (XIII) to afford carboxamide (XX). The condensation of (XX) with veratrole (VI) by means of BuLi as before yields the ketonic precursor (XVII), which is finally reduced as before. 4) [11C]-Radiolabeled MDL-100907 can be obtained as follows: Racemic MDL-100907 (VII) is treated with L-Selectride in THF, yielding racemic 1-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]-1-(3-hydroxy-2-methoxy-phenyl)methanol (rac-XXI), which is submitted to semi-preparative HPLC separation over Chiracel OD, affording pure (R-XXI). Finally, this compound is methylated with [11C]-methyl iodide and KOH in HMPA. If this methylation is performed with nonlabeled methyl iodide, MDL-100907 is obtained. 5) The radiolabeling of phenol (R-XXI) can also be performed with better yields using [11C]-methyl trifluoromethanesulfonate (XXII) as methylating agent. Triflate (XXII) is obtained by reaction of silver triflate with [11C]-methyl iodide.
| 【1】 Mathis, C.A.; Mahmood, K.; Price, J.C.; Huang, Y.; Gerdes, J.M.; Simpson, N.R.; Synthesis and preliminary in vivo evaluation of [11C]MDL 100907: A potent and selective radioligand for the 5-HT2A receptor system. Med Chem Res 1996, 6, 1, 1-10. |
| 【2】 Castaner, J.; Sorbera, L.A.; Silvestre, J.S.; MDL-100907. Drugs Fut 1998, 23, 9, 955. |
| 【3】 Hiyama, T.; Minami, T.; Hanamoto, T.; Reddy, G.B. (Sagami Chemical Research Center); Optically active esters of 7-substd. 3,5-difunctionalized 6-heptenoic acids. EP 0475627 . |
| 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) | 17394 | 1-(2-bromoethyl)-4-fluorobenzene | C8H8BrF | 详情 | 详情 | |
| (VI) | 17398 | 2-methoxyphenyl methyl ether; Veratrole; 1,2-dimethoxybenzene | 91-16-7 | C8H10O2 | 详情 | 详情 |
| (VII) | 17399 | (2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanol | C22H28FNO3 | 详情 | 详情 | |
| (XIII) | 13361 | (Methoxyamino)methane; N,O-Dimethylhydroxylamine | 1117-97-1 | C2H7NO | 详情 | 详情 |
| (XVII) | 17409 | (2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanone | C22H26FNO3 | 详情 | 详情 | |
| (XVIII) | 17410 | Ethyl isonipecotate; ethyl 4-piperidinecarboxylate | 1126-09-6 | C8H15NO2 | 详情 | 详情 |
| (XIX) | 17411 | ethyl 1-(4-fluorophenethyl)-4-piperidinecarboxylate | C16H22FNO2 | 详情 | 详情 | |
| (XX) | 17412 | 1-(4-fluorophenethyl)-N-methoxy-N-methyl-4-piperidinecarboxamide | C16H23FN2O2 | 详情 | 详情 | |
| (XXI) | 17413 | 3-[(R)-[1-(4-fluorophenethyl)-4-piperidinyl](hydroxy)methyl]-2-methoxyphenol | C21H26FNO3 | 详情 | 详情 | |
| (XXII) | 17414 | methyl trifluoromethane sulfonate; methyl trifluoromethanesulfonate | 333-27-7 | C2H3F3O3S | 详情 | 详情 |
| (XXII) | 45233 | methyl trifluoromethanesulfonate | C2H3F3O3S | 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 condensation of 1,2-dimethoxybenzene (I) with 1-(tert-butoxcarbonyl)-N-methoxy-N-methylpiperidine-4-carboxamide (II) by means of BuLi in THF gives the protected benzoylpiperidine (III), which is deprotected by means of TFA to yield the deprotected piperidine (IV). The reduction of the carbonyl group of (IV) by means of NaBH4 in methanol affords the racemic carbinol (V), which is submitted to optical resolution with (+)-di-O,O'-p-toluyltartaric acid, providing the (+)-(R)-carbinol (VI). Finally, this compound is condensed with 2-(4-fluorophenyl)ethyl bromide (VIII) by means of NaHCO3 in hot DMF.
| 【1】 Ullrich, T.; Rice, K.C.; A practical synthesis of the serotonin 5-HT2A receptor antagonist MDL-100907, its enantiomer and their 3-phenolic derivatives as precursors for [11C]labeled PET ligands. Bioorg Med Chem 2000, 8, 10, 2427. |
| 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) | 17398 | 2-methoxyphenyl methyl ether; Veratrole; 1,2-dimethoxybenzene | 91-16-7 | C8H10O2 | 详情 | 详情 |
| (II) | 17406 | tert-butyl 4-[[methoxy(methyl)amino]carbonyl]tetrahydro-1(2H)-pyridinecarboxylate | C13H24N2O4 | 详情 | 详情 | |
| (III) | 17407 | tert-butyl 4-(2,3-dimethoxybenzoyl)tetrahydro-1(2H)-pyridinecarboxylate | C19H27NO5 | 详情 | 详情 | |
| (IV) | 17408 | (2,3-dimethoxyphenyl)(4-piperidinyl)methanone | C14H19NO3 | 详情 | 详情 | |
| (V) | 52803 | (2,3-dimethoxyphenyl)(4-piperidinyl)methanol | C14H21NO3 | 详情 | 详情 | |
| (VI) | 52804 | (R)-(2,3-dimethoxyphenyl)(4-piperidinyl)methanol | C14H21NO3 | 详情 | 详情 | |
| (VII) | 17394 | 1-(2-bromoethyl)-4-fluorobenzene | C8H8BrF | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(I)Treatment of veratrole (I) with aqueous HNO3 and H2SO4 yields 1,2-dinitrobenzene derivative (II), which is then converted into diamine (III) by hydrogenation over Pd/C in HOAc/EtOH or over PtO2. Finally, reaction of diamine (III) with phenyl glyoxal (IV) in EtOH and HOAc or HCl affords the desired product.
| 【1】 Bohmer, F.D.; Chen, J.; Gazit, A.; McMahon, G.; Levitzki, A.; App, H.; Tyrphostins. 5. Potent inhibitors of platelet-derived growth factor receptor tyrosine kinase: Structure-activity relationships in quinoxalines, quinolines, and indole tyrphostins. J Med Chem 1996, 39, 11, 2170. |
| 【2】 Treatment of platelet derived growth factor related disorders such as cancers using inhibitors of platelet derived growth receptor. EP 1000617; US 5700823; WO 9519169 . |
| 【3】 Levitzki, A.; Hirth, K.P.; Schwartz, D.P.; Tang, P.C.; Ullrich, A.; Haimichael, J.; Shawver, L.K.; Szekely, I.; Mann, E.; Orfi, L.; Slamon, D.; Keri, G.; Kabbinavar, F.F.; Gazit, A.; Bajor, T.; Lammers, R. (Sugen, Inc.); Treatment of platelet derived growth factor related disorders such as cancers. US 5990141 . |
| 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) | 17398 | 2-methoxyphenyl methyl ether; Veratrole; 1,2-dimethoxybenzene | 91-16-7 | C8H10O2 | 详情 | 详情 |
| (II) | 43039 | 2-methoxy-4,5-dinitrophenyl methyl ether; 1,2-dimethoxy-4,5-dinitrobenzene | 3395-03-7 | C8H8N2O6 | 详情 | 详情 |
| (III) | 34621 | 4,5-dimethoxy-1,2-benzenediamine; 2-amino-4,5-dimethoxyphenylamine | C8H12N2O2 | 详情 | 详情 | |
| (IV) | 43040 | 2-oxo-2-phenylacetaldehyde | C8H6O2 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(X)A new enantioselective synthesis of A-86929, the active form of the diacetyl prodrug ABT-431 has been published: The condensation of 4-bromo-2-propylthiophene (I) with 4-(3,4-dimethoxyphenyl)-N-methoxy-N-methyl-2(R)-(trifluoroacetamido)butyramide (II) by means of butyllithium in ethyl ether gives 4-(3,4-dimethoxyphenyl)-1-(5-propyl-3-thienyl)-2(R)-(trifluoroacetamido)-1-butanone (III), which is reduced with NaBH4 in ethanol yielding 4-(3,4-dimethoxyphenyl)-1-(5-propyl-3-thienyl)-2(R)-(trifluoroacetamido-1(S)-butanol (IV) in a 4:1 ratio with its diastereomeric alcohol. The cyclization of (IV) with SnCl4 in dichloromethane affords the substituted tetraline (V), which is treated with K2CO3 in methanol/water to give (1S,2R)-6,7-dimethoxy-1-(5-propyl-3-thienyl)-1,2,3,4-tetrahydro-2-naphthylamine (VI). The cyclization of (VI) with formaldehyde and HCl in refluxing ethanol yields the tetracyclic intermediate (VII), which is finally demethylated with BBr3 in dichloromethane. The two starting compounds (I) and (II) have been obtained as follows: 1) The bromination of 1-(2-thienyl)-1-propanone (VIII) with Br2/AlCl3 in chloroform gives 1-(4-bromo-2-thienyl)-1-propanone (IX), which is then reduced to (I) with hydrazine and KOH in ethylene glycol at 160 C. 2) The Friedel Craft's condensation of 1,2-dimethoxybenzene (X) with 2(R)-(trifluoroacetamido)succinic anhydride (XI) by means of AlCl3 gives 4-(3,4-dimethoxyphenyl)-4-oxo-2(R)-(trifluoroacetamido)butyric acid (XII), which is reduced with H2 over Pd/C in HCl/isopropanol yielding 4-(3,4-dimethoxyphenyl)-2(R)-(trifluoroacetamido)butyric acid (XIII). Finally, this compound is condensed with N,O-dimethylhydroxylamine by means of isobutyl chloroformate and N-methylmorpholine (NMM) in THF affording amide (II).
| 【1】 Ehrlich, P.P.; Ralston, J.W.; Michaelides, M.R.; An efficient enantioselective synthesis of the D1 agonist (5aR,11bS)-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclo-penta[c]phenanthrene-9,10-diol (A-86929). J Org Chem 1997, 62, 9, 2782. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 65063 | N-{(1R)-3-(3,4-dimethoxyphenyl)-1-[(R)-hydroxy(5-propyl-3-thienyl)methyl]propyl}-2,2,2-trifluoroacetamide | C21H26F3NO4S | 详情 | 详情 | ||
| (I) | 17535 | 4-bromo-2-propylthiophene | 36155-79-0 | C7H9BrS | 详情 | 详情 |
| (II) | 17536 | (2R)-4-(3,4-dimethoxyphenyl)-N-methoxy-N-methyl-2-[(2,2,2-trifluoroacetyl)amino]butanamide | C16H21F3N2O5 | 详情 | 详情 | |
| (III) | 17537 | N-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(5-propyl-3-thienyl)carbonyl]propyl]-2,2,2-trifluoroacetamide | C21H24F3NO4S | 详情 | 详情 | |
| (IV) | 17538 | N-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(S)-hydroxy(5-propyl-3-thienyl)methyl]propyl]-2,2,2-trifluoroacetamide | C21H26F3NO4S | 详情 | 详情 | |
| (V) | 17539 | N-[(1S,2R)-6,7-dimethoxy-1-(5-propyl-3-thienyl)-1,2,3,4-tetrahydro-2-naphthalenyl]-2,2,2-trifluoroacetamide | C21H24F3NO3S | 详情 | 详情 | |
| (VI) | 16970 | (1S,2R)-6,7-dimethoxy-1-(5-propyl-3-thienyl)-1,2,3,4-tetrahydro-2-naphthalenylamine; (1S,2R)-6,7-dimethoxy-1-(5-propyl-3-thienyl)-1,2,3,4-tetrahydro-2-naphthalenamine | C19H25NO2S | 详情 | 详情 | |
| (VII) | 16971 | (rac)-(5aR*,11bS*)-10-methoxy-2-propyl-4,5,5a,6,7,11b-hexahydrobenzo[f]thieno[2,3-c]quinolin-9-yl methyl ether; (rac)-(5aR*,11bS*)-9,10-dimethoxy-2-propyl-4,5,5a,6,7,11b-hexahydrobenzo[f]thieno[2,3-c]quinoline | C20H25NO2S | 详情 | 详情 | |
| (VIII) | 17542 | 1-(2-thienyl)-1-propanone | 13679-75-9 | C7H8OS | 详情 | 详情 |
| (IX) | 17543 | 1-(4-bromo-2-thienyl)-1-propanone | C7H7BrOS | 详情 | 详情 | |
| (X) | 17398 | 2-methoxyphenyl methyl ether; Veratrole; 1,2-dimethoxybenzene | 91-16-7 | C8H10O2 | 详情 | 详情 |
| (XI) | 17545 | N-[(3R)-2,5-dioxotetrahydro-3-furanyl]-2,2,2-trifluoroacetamide | C6H4F3NO4 | 详情 | 详情 | |
| (XII) | 17546 | (2R)-4-(3,4-dimethoxyphenyl)-4-oxo-2-[(2,2,2-trifluoroacetyl)amino]butyric acid | C14H14F3NO6 | 详情 | 详情 | |
| (XIII) | 17547 | (2R)-4-(3,4-dimethoxyphenyl)-2-[(2,2,2-trifluoroacetyl)amino]butyric acid | C14H16F3NO5 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(I)Direct amination of veratrole (I) with lithium dimethylamide produces 2-methoxy-N,N-dimethylaniline (II). The title ammonium salt is then prepared by quaternization of the tertiary amine (II) with allyl bromide (III).
| 【1】 Tarver, G.J.; Kaur, J.; Zhang, M.-Q.; Pow, E.; Muir, A.W.; Grove, S.J.A.; Oxyaniliniums as acetylcholinesterase inhibitors for the reversal of neuromuscular block. Bioorg Med Chem Lett 2002, 12, 2, 193. |
| 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) | 17398 | 2-methoxyphenyl methyl ether; Veratrole; 1,2-dimethoxybenzene | 91-16-7 | C8H10O2 | 详情 | 详情 |
| (II) | 59068 | N-(2-methoxyphenyl)-N,N-dimethylamine; 2-methoxy-N,N-dimethylaniline | C9H13NO | 详情 | 详情 | |
| (III) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |