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【结 构 式】 
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【分子编号】25239 【品名】3-chloroaniline; 3-chlorophenylamine 【CA登记号】108-42-9 |
【 分 子 式 】C6H6ClN 【 分 子 量 】127.57308 【元素组成】C 56.49% H 4.74% Cl 27.79% N 10.98% |
合成路线1
该中间体在本合成路线中的序号：(X)The reaction of 3-chloroaniline (X) with choral hydrate (XI) and hydroxylamine gives isonitroso-3-chloroacetanilide (XII), which is cyclized by means of H2SO4 to 4-chloroisatin (XIII). Chlorination of (XIII) with SO2Cl2 affords 4,5-dichloroisatin (XIV), which is oxidized with H2O2 yielding 5,6-dichloroanthranilic acid (XV). The reduction of (XV) with borane in THF gives 6-amino-2,3-dichlorobenzyl alcohol (XVI), which by reaction with SOCl2 in benzene is converted to 6-amino-2,3-dichlorobenzyl chloride (XVII). This compound is condensed with ethyl glycinate (XVIII) by means of triethylamine in refluxing methylene chloride to give ethyl N-(6-amino-2,3-dichlorobenzyl)glycinate (VII), which is cyclized with cyanogen bromide (VIII) in toluene affording ethyl 5,6-dichloro-3,4-dihydro-2-(1H)-iminoquinazoline-3-acetate (IX). Finally, this compound is submitted to a new cyclization by means of triethylamine in refluxing ethanol.
| 【1】 Jenks, T.A.; Beverung, W.N.Jr.; Partyka, R.A. (Bristol-Myers Squibb Co.); Preparation of 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-one. CA 1137474 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 29087 | ethyl 2-[(6-amino-2,3-dichlorobenzyl)amino]acetate | C11H14Cl2N2O2 | 详情 | 详情 | |
| (VIII) | 28017 | cyanic bromide；cyanogen bromide | 506-68-3 | CBrN | 详情 | 详情 |
| (IX) | 29088 | ethyl 2-[5,6-dichloro-2-imino-1,4-dihydro-3(2H)-quinazolinyl]acetate | C12H13Cl2N3O2 | 详情 | 详情 | |
| (X) | 25239 | 3-chloroaniline; 3-chlorophenylamine | 108-42-9 | C6H6ClN | 详情 | 详情 |
| (XI) | 14018 | 2,2,2-Trichloro-1,1-ethanediol; Chloral hydrate | 302-17-0 | C2H3Cl3O2 | 详情 | 详情 |
| (XII) | 29089 | N-(3-chlorophenyl)-2-(hydroxyimino)acetamide | C8H7ClN2O2 | 详情 | 详情 | |
| (XIII) | 29090 | 4-chloro-1H-indole-2,3-dione | C8H4ClNO2 | 详情 | 详情 | |
| (XIV) | 29091 | 4,5-dichloro-1H-indole-2,3-dione | C8H3Cl2NO2 | 详情 | 详情 | |
| (XV) | 29092 | 6-amino-2,3-dichlorobenzoic acid | C7H5Cl2NO2 | 详情 | 详情 | |
| (XVI) | 29093 | (6-amino-2,3-dichlorophenyl)methanol | C7H7Cl2NO | 详情 | 详情 | |
| (XVII) | 29094 | 3,4-dichloro-2-(chloromethyl)aniline | C7H6Cl3N | 详情 | 详情 | |
| (XVIII) | 10309 | ethyl 2-aminoacetate; Glycine ethyl ester | 459-73-4 | C4H9NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)By condensation of 1-chloro-4-phenylphthalazine (I) with 3-chloroaniline (II) by means of powdered Cu at 100 C.
| 【1】 Hayashi, E.; Oishi, E.; Marinaka, Y.; Mori, M.; Kanayama, T. (Mitsubishi Chemical Corp.); 4-Phenylphthalazine derivs.. GB 2063249 . |
| 【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; MY-5445. Drugs Fut 1983, 8, 6, 507. |
合成路线3
该中间体在本合成路线中的序号：(IV)The acetylation of 1,2,3,4-tetrahydroisoquinoline (I) with acetic anhydride gives 2-acetyl-1,2,3,4-tetrahydroisoquinoline (II), which is sulfonated with chloro sulfonic acid in methylene chloride yielding 2-acetyl-7-chlorosulfonyl-1,2,3,4-tetrahydroisoquinoline (III). The reaction of (III) with 3-chloroaniline (IV) and triethylamine in refluxing acetone affords 2-acetyl-7-(3-chlorophenylamino sulfonyl)-1,2,3,4-tetrahydroisoquinoline (V), which is deacetylated by a treatment with HCl in refluxing butanol to 7-(3-chlorophenylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (VI). Finally, this compound is condensed with bis(chlorosulfonyl)imide (VII) [prepared with chlorosulfonic acid (VIII) and chlorosulfonyl isocyanate (IX)] in acetonitrile containing triethylamine.
| 【1】 Ali Fadia E. (SmithKline Beecham Corp.); N,N'-Bis[substituted-1,2,3,4-tetrahydroisoquinolino]disulfonylimides and antiallergic compositions and method of use. DD 158240; EP 0038177; US 4135935 . |
| 【2】 Serradell, M.N.; Chu, S.S.; Castaner, J.; SKF-88046. Drugs Fut 1985, 10, 1, 42. |
| 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) | 14124 | 1,2,3,4-Tetrahydroisoquinoline | 91-21-4 | C9H11N | 详情 | 详情 |
| (II) | 29003 | 1-[3,4-dihydro-2(1H)-isoquinolinyl]-1-ethanone | C11H13NO | 详情 | 详情 | |
| (III) | 29004 | 2-acetyl-1,2,3,4-tetrahydro-7-isoquinolinesulfonyl chloride | C11H12ClNO3S | 详情 | 详情 | |
| (IV) | 25239 | 3-chloroaniline; 3-chlorophenylamine | 108-42-9 | C6H6ClN | 详情 | 详情 |
| (V) | 29005 | 2-acetyl-N-(3-chlorophenyl)-1,2,3,4-tetrahydro-7-isoquinolinesulfonamide | C17H17ClN2O3S | 详情 | 详情 | |
| (VI) | 29006 | N-(3-chlorophenyl)-1,2,3,4-tetrahydro-7-isoquinolinesulfonamide | C15H15ClN2O2S | 详情 | 详情 | |
| (VII) | 29007 | Bis(chlorosulfonyl)imide | HCl2NO4S2 | 详情 | 详情 | |
| (VIII) | 29008 | Chlorosulfonic acid | 7790-94-5 | HClO3S | 详情 | 详情 |
| (IX) | 14101 | Chlorosulfonyl isocyanate | 1189-71-5 | CClNO3S | 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 acetylation of 3-chloroaniline (I) with refluxing acetic anhydride gives the corresponding anilide (II), which is nitrated with HNO3/H2SO4 yielding 5-chloro-2-nitroacetanilide (III). The hydrolysis of (III) with hot conc. H2SO4 affords 5-chloro-2-nitroaniline (IV), which is treated with NaNO2/HCl to afford the corresponding diazonium salt (V). The reaction of (V) with sodium azide gives 2-nitro-5-chlorophenylazide (VI), which is cyclized to 5-chlorobenzofurazan-3-oxide (VII) in refluxing toluene. The condensation of (VII) with malononitrile (VIII) in DMF in the presence of a catalytic amount of triethylamine afforded a mixture of the isomeric quinoxaline-di-N-oxides (IX and X), which were separated by flash chromatography. The 7-chloro isomer (XI) was then submitted to diazotization with tert-butyl nitrite in acetonitrile in the presence of cupric chloride, which effected a Sandmeyer reaction to give the 2,6-dichloro derivative (XI). N-Alkylation of 3-(N,N-dimethylamino)propylamine (XII) with intermediate (XI) in dichloromethane in the presence of potassium carbonate, followed by treatment with concentrated hydrochloric acid in acetone afforded the title compound.
| 【1】 Monge, A.; et al.; Hypoxia-selective agents derived from quinoxaline 1, 4-di-N-oxides. J Med Chem 1995, 38, 10, 1786. |
| 【2】 Monge, A.; et al.; Hypoxia-selective agents derived from 2-quinoxalinecarbonitrile 1,4-di-N-oxides. 2. J Med Chem 1995, 38, 22, 4488. |
| 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) | 25239 | 3-chloroaniline; 3-chlorophenylamine | 108-42-9 | C6H6ClN | 详情 | 详情 |
| (II) | 25240 | N-(3-chlorophenyl)acetamide | 588-07-8 | C8H8ClNO | 详情 | 详情 |
| (III) | 25241 | N-(5-chloro-2-nitrophenyl)acetamide | 39163-92-3 | C8H7ClN2O3 | 详情 | 详情 |
| (IV) | 15709 | 5-chloro-2-nitrophenylamine; 5-chloro-2-nitroaniline | 1635-61-6 | C6H5ClN2O2 | 详情 | 详情 |
| (V) | 25242 | 5-chloro-2-nitrobenzenediazonium chloride | 2589-71-1 | C6H3Cl2N3O2 | 详情 | 详情 |
| (VI) | 25243 | 2-azido-4-chloro-1-nitrobenzene | C6H3ClN4O2 | 详情 | 详情 | |
| (VII) | 25244 | 7-chloro-4a,8a-dihydro-1-quinoliniumolate | C9H8ClNO | 详情 | 详情 | |
| (VIII) | 12061 | Malononitrile | 109-77-3 | C3H2N2 | 详情 | 详情 |
| (IX) | 25245 | 2-amino-6-chloro-3-cyano-1,4-quinoxalinediiumdiolate | C9H5ClN4O2 | 详情 | 详情 | |
| (X) | 25246 | 3-amino-6-chloro-2-cyano-1,4-quinoxalinediiumdiolate | C9H5ClN4O2 | 详情 | 详情 | |
| (XI) | 25247 | 2,6-dichloro-3-cyano-1,4-quinoxalinediiumdiolate | C9H3Cl2N3O2 | 详情 | 详情 | |
| (XII) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(VIII)Pyrimidinyl pyrazole (III) was prepared by condensation of diketone (I) with 2-hydrazinopyrimidine (II). Subsequent Mannich reaction with N-(3-chlorophenyl)piperazine (IV) and paraformaldehyde furnished piperazinyl propanone (V). This was reduced to alcohol (VI) with NaBH4. Alcohol dehydration employing p-toluenesulfonic acid yielded the title compound, that was finally isolated as the hydrochloride salt. The intermediate N-(3-chlorophenyl)piperazine (IV) has been obtained by cyclization of bis(2-chloroethyl)amine (VII) with 3-chloroaniline (VIII) by means of Na2CO3 in refluxing butanol.
| 【1】 DE 2038503; US 3723433 . |
| 【2】 Ejima, A.; Sugimori, M.; Mitsui, I. (Daiichi Pharmaceutical Co., Ltd.); Pyrimidinylpyrazole deriv.. EP 0784055; JP 1997048776; US 5852019; WO 9610024 . |
| 【3】 Ishii, M.; Ejima, A.; Hirotani, K.; Iwahana, M.; Sugimori, M.; Mitsui, I.; Naito, H.; Nakamura, Y.; Synthesis and antitumor activity of novel pyrimidinyl pyrazole derivatives. Chem Pharm Bull 1999, 47, 12, 1679. |
| 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) | 41449 | 3-(ethoxymethylene)-2,4-pentanedione | C8H12O3 | 详情 | 详情 | |
| (II) | 41450 | 2-hydrazinopyrimidine | C4H6N4 | 详情 | 详情 | |
| (III) | 41451 | 1-[5-methyl-1-(2-pyrimidinyl)-1H-pyrazol-4-yl]-1-ethanone | C10H10N4O | 详情 | 详情 | |
| (IV) | 22114 | 1-(3-chlorophenyl)piperazine | 6640-24-0 | C10H13ClN2 | 详情 | 详情 |
| (V) | 41452 | 3-[4-(3-chlorophenyl)-1-piperazinyl]-1-[5-methyl-1-(2-pyrimidinyl)-1H-pyrazol-4-yl]-1-propanone | C21H23ClN6O | 详情 | 详情 | |
| (VI) | 41453 | 3-[4-(3-chlorophenyl)-1-piperazinyl]-1-[5-methyl-1-(2-pyrimidinyl)-1H-pyrazol-4-yl]-1-propanol | C21H25ClN6O | 详情 | 详情 | |
| (VII) | 21583 | 2-chloro-N-(2-chloroethyl)-1-ethanamine; Bis(2-chloroethyl)amine; 1,1'-iminobis(2-chloroethane); N,N-bis(2-chloroethyl)amine | 821-48-7 | C4H9Cl2N | 详情 | 详情 |
| (VIII) | 25239 | 3-chloroaniline; 3-chlorophenylamine | 108-42-9 | C6H6ClN | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(I)The reductive alkylation of 3-chloroaniline (I) with L-S-trityl-N-Boc-cysteinal (II) in the presence of sodium triacetoxyborohydride produced amine (III). Chloroacetylation of (III) followed by cesium carbonate-induced cyclization of the resulting chloroacetamide (IV) furnished the protected piperazinone (V). The S-trityl group of (V) was deprotected by treatment with silver nitrate and pyridine, yielding thiol (VI), which was subsequently alkylated with ethyl iodide to give thioether (VII). Sulfur oxidation by means of magnesium monoperoxyphthalate in methanol afforded sulfone (VIII). Then, acid deprotection of the Boc protecting group of (VIII) provided the intermediate piperazinone (IX).
| 【1】 Anthony, N.J.; Ciccarone, T.M.; Gomez, R.P.; Hutchinson, J.H.; Williams, T.M.; Dinsmore, C.J.; Stokker, G.E. (Merck & Co., Inc.); Inhibitors of farnesyl-protein transferase. EP 0820445; JP 1998511098; US 5856326; WO 9630343 . |
| 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) | 25239 | 3-chloroaniline; 3-chlorophenylamine | 108-42-9 | C6H6ClN | 详情 | 详情 |
| (II) | 17953 | tert-butyl (1R)-1-formyl-2-(tritylsulfanyl)ethylcarbamate | C27H29NO3S | 详情 | 详情 | |
| (III) | 42109 | tert-butyl (1R)-2-(3-chloroanilino)-1-[(tritylsulfanyl)methyl]ethylcarbamate | C33H35ClN2O2S | 详情 | 详情 | |
| (IV) | 42110 | tert-butyl (1R)-2-[3-chloro(2-chloroacetyl)anilino]-1-[(tritylsulfanyl)methyl]ethylcarbamate | C35H36Cl2N2O3S | 详情 | 详情 | |
| (V) | 42111 | tert-butyl (2R)-4-(3-chlorophenyl)-5-oxo-2-[(tritylsulfanyl)methyl]-1-piperazinecarboxylate | C35H35ClN2O3S | 详情 | 详情 | |
| (VI) | 42112 | tert-butyl (2R)-4-(3-chlorophenyl)-5-oxo-2-(sulfanylmethyl)-1-piperazinecarboxylate | C16H21ClN2O3S | 详情 | 详情 | |
| (VII) | 42113 | tert-butyl (2R)-4-(3-chlorophenyl)-2-[(ethylsulfanyl)methyl]-5-oxo-1-piperazinecarboxylate | C18H25ClN2O3S | 详情 | 详情 | |
| (VIII) | 42114 | tert-butyl (2R)-4-(3-chlorophenyl)-2-[(ethylsulfonyl)methyl]-5-oxo-1-piperazinecarboxylate | C18H25ClN2O5S | 详情 | 详情 | |
| (IX) | 42115 | (5R)-1-(3-chlorophenyl)-5-[(ethylsulfonyl)methyl]-2-piperazinone | C13H17ClN2O3S | 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 synthesis of the intermediate (chlorophenyl)piperazinone (VIII) has been reported by two procedures. The hydrochloride salt prepared from 3-chloroaniline (I) was treated with 2-oxazolidinone (II) at 160 C to produce the aryl ethylenediamine (III), which was subsequently protected as the N-Boc derivative (IV). Acylation of aniline (IV) with chloroacetyl chloride (V) gave the chloroacetamide (VI). This was then cyclized to the piperazinone (VII) by treatment with K2CO3 in hot DMF. Further acid deprotection of the Boc group of (VII) afforded the intermediate (VIII).
| 【1】 Anthony, N.J.; Ciccarone, T.M.; Gomez, R.P.; Hutchinson, J.H.; Williams, T.M.; Dinsmore, C.J.; Stokker, G.E. (Merck & Co., Inc.); Inhibitors of farnesyl-protein transferase. EP 0820445; JP 1998511098; US 5856326; WO 9630343 . |
| 【2】 Williams, T.M.; Dinsmore, C.J.; Hutchinson, J.H. (Merck & Co., Inc.); Inhibitors of prenyl-protein transferase. EP 1014984; WO 9909985 . |
| 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) | 25239 | 3-chloroaniline; 3-chlorophenylamine | 108-42-9 | C6H6ClN | 详情 | 详情 |
| (II) | 21456 | 1,3-oxazolidin-2-one | 497-25-6 | C3H5NO2 | 详情 | 详情 |
| (III) | 37091 | C7H5Cl2FNO2P | 详情 | 详情 | ||
| (IV) | 47286 | tert-butyl 2-(3-chloroanilino)ethylcarbamate | C13H19ClN2O2 | 详情 | 详情 | |
| (V) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
| (VI) | 47287 | tert-butyl 2-[3-chloro(2-chloroacetyl)anilino]ethylcarbamate | C15H20Cl2N2O3 | 详情 | 详情 | |
| (VII) | 47288 | tert-butyl 4-(3-chlorophenyl)-3-oxo-1-piperazinecarboxylate | C15H19ClN2O3 | 详情 | 详情 | |
| (VIII) | 47289 | 1-(3-chlorophenyl)-2-piperazinone | C10H11ClN2O | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(I)In an alternative procedure, 3-chloroaniline (I) was acylated with chloroacetyl chloride (V) to produce chloroacetamide (IX). Displacement of the chloride group of (IX) with ethanolamine (X) gave rise to the amide alcohol (XI), which was then cyclized to the piperazinone (VIII) under Mitsunobu conditions.
| 【1】 Cowen, J.A.; Askin, D.; McWilliams, J.C.; Maligres, P.E.; McCauley, J.A. (Merck & Co., Inc.); Process for making farnesyl-protein transferase inhibitors. WO 0001691 . |
| 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) | 25239 | 3-chloroaniline; 3-chlorophenylamine | 108-42-9 | C6H6ClN | 详情 | 详情 |
| (V) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
| (VIII) | 47289 | 1-(3-chlorophenyl)-2-piperazinone | C10H11ClN2O | 详情 | 详情 | |
| (IX) | 47290 | 2-chloro-N-(3-chlorophenyl)acetamide | C8H7Cl2NO | 详情 | 详情 | |
| (X) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |
| (XI) | 47291 | N-(3-chlorophenyl)-2-[(2-hydroxyethyl)amino]acetamide | C10H13ClN2O2 | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(II)Condensation of 2,6-dichloropurine (I) with 3-chloroaniline (II) in hot pentanol yielded the 6-anilino purine (III). This was then alkylated at the N-9 with iodoethane and K2CO3 to afford (IV). Finally, displacement of the 2-chloro of (IV) with cis-1,2-cyclohexanediamine (V) at 150 C furnished the title compound.
| 【1】 Imbach, P.; Capraro, H.G.; Furet, P.; Mett, H.; Meyer, T.; Zimmermann, J.; 2,6,9-Trisubstituted purines: Optimization towards highly potent and selective CDK1 inhibitors. Bioorg Med Chem Lett 1999, 9, 1, 91. |
| 【2】 Capraro, H.-G.; Zimmermann, J.; Furet, P.; Peterli, P. (Novartis AG); Purine derivs. and processes for their preparation. JP 1999514336; WO 9716452 . |
| 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) | 25254 | 2,6-dichloro-9H-purine | 5451-40-1 | C5H2Cl2N4 | 详情 | 详情 |
| (II) | 25239 | 3-chloroaniline; 3-chlorophenylamine | 108-42-9 | C6H6ClN | 详情 | 详情 |
| (III) | 59602 | 2-chloro-N-(3-chlorophenyl)-9H-purin-6-amine; N-(3-chlorophenyl)-N-(2-chloro-9H-purin-6-yl)amine | C11H7Cl2N5 | 详情 | 详情 | |
| (IV) | 59603 | 2-chloro-N-(3-chlorophenyl)-9-ethyl-9H-purin-6-amine; N-(2-chloro-9-ethyl-9H-purin-6-yl)-N-(3-chlorophenyl)amine | C13H11Cl2N5 | 详情 | 详情 | |
| (V) | 37409 | (1R,2S)-2-aminocyclohexylamine; (1R,2S)-1,2-cyclohexanediamine | 1121-22-8 | C6H14N2 | 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 reaction of 3-chloroaniline (I) with ethanolamine (II) by means of 47% HBr by heating at 170 C gives N-(3-chlorophenyl)ethylenediamine (III), which is condensed with ethyl 2-bromopropionate (IV) by means of triethylamine in refluxing toluene yielding the alanine derivative (V). The cyclization of (V) with refluxing 2N HCl affords the piperazinone (VI), which is reduced with LiAlH4 in ethyl ether providing 1-(3-chlorophenyl)-3-methylpiperazine (VII). The alkylation of (VII) with 1-bromo-3-chloropropane (VIII) by means of NaOH in acetone/water gives 4-(3-chlorophenyl)-1-(3-chloropropyl)-2-methylpiperazine (IX), which is condensed with the sodium salt of 1,2,4-triazolo[4,3-a]pyridin-3(2H)-one (X) in refluxing xylene/isobutanol yielding the target compound as a racemic mixture (XI). Finally, this compound is submitted to optical resolution with L-(+)-tartaric acid (XII).
| 【1】 Giannangeli, M.; Gazzolla, N.; Luparini, M.R.; Magnani, M.; Mabilia, M.; Picconi, G.; Tomaselli, M.; Baiocchi, L.; Effect of modifications of the alkylpiperazine moiety of trazodone on 5HT2A and alpha1 receptor binding affinity. J Med Chem 1999, 42, 3, 336. |
| 【2】 Baiocchi, L.; Cioli, V. (Angelini Group); Pharmacologically active enantiomers. EP 0707587; JP 1996512036; WO 9501354 . |
| 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) | 25239 | 3-chloroaniline; 3-chlorophenylamine | 108-42-9 | C6H6ClN | 详情 | 详情 |
| (II) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |
| (III) | 34091 | N(1)-(3-chlorophenyl)-1,2-ethanediamine; N-(2-aminoethyl)-N-(3-chlorophenyl)amine | C8H11ClN2 | 详情 | 详情 | |
| (IV) | 19460 | ethyl 2-bromopropanoate; 2-Bromopropionic acid ethyl ester | 535-11-5 | C5H9BrO2 | 详情 | 详情 |
| (V) | 28373 | ethyl 2-[[2-(3-chloroanilino)ethyl]amino]propanoate | C13H19ClN2O2 | 详情 | 详情 | |
| (VI) | 28374 | 1-(3-chlorophenyl)-3-methyl-2-piperazinone | C11H13ClN2O | 详情 | 详情 | |
| (VII) | 28375 | 1-(3-chlorophenyl)-3-methylpiperazine | C11H15ClN2 | 详情 | 详情 | |
| (VIII) | 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 |
| (IX) | 28376 | 4-(3-chlorophenyl)-1-(3-chloropropyl)-2-methylpiperazine | C14H20Cl2N2 | 详情 | 详情 | |
| (X) | 28377 | [3-oxo[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl]sodium | C6H4N3NaO | 详情 | 详情 | |
| (XI) | 28378 | 2-[3-[4-(3-chlorophenyl)-2-methyl-1-piperazinyl]propyl][1,2,4]triazolo[4,3-a]pyridin-3(2H)-one | C20H24ClN5O | 详情 | 详情 | |
| (XII) | 28379 | (2R,3R)-2,3-dihydroxybutanedioic acid; L-Tartaric acid; (2R,3R)-2,3-dihydroxysuccinic acid | 87-69-4 | C4H6O6 | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(I)3-Chloroaniline (I) was acylated with chloroacetyl chloride (II) in isopropyl acetate. The resulting chloroacetanilide (III) was condensed with ethanolamine (IV) to yield the (hydroxyethyl)glycinamide (V). Cyclization of (V) to produce the piperazinone (VI) was then effected by treatment with di-tert-butyl azodicarboxylate and tributylphosphine.
| 【1】 Williams, T.M. (Merck & Co., Inc.); Biaryl inhibitors of prenyl-protein transferase. WO 0075135 . |
| 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) | 25239 | 3-chloroaniline; 3-chlorophenylamine | 108-42-9 | C6H6ClN | 详情 | 详情 |
| (II) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
| (III) | 47290 | 2-chloro-N-(3-chlorophenyl)acetamide | C8H7Cl2NO | 详情 | 详情 | |
| (IV) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |
| (V) | 47291 | N-(3-chlorophenyl)-2-[(2-hydroxyethyl)amino]acetamide | C10H13ClN2O2 | 详情 | 详情 | |
| (VI) | 47289 | 1-(3-chlorophenyl)-2-piperazinone | C10H11ClN2O | 详情 | 详情 |