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【结 构 式】 
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【分子编号】28542 【品名】N-Benzylpiperazine; 1-Benzylpiperazine 【CA登记号】2759-28-6 |
【 分 子 式 】C11H16N2 【 分 子 量 】176.26152 【元素组成】C 74.96% H 9.15% N 15.89% |
合成路线1
该中间体在本合成路线中的序号：(II)Coumarilic acid is reacted with N-benzylpiperazine (II) by two different ways: a) The acid chloride (I) is treated with (II) in the presence of a further base to give (III) or without a base in boiling dimethylformamide. b) The coumarilic acid salt of N-benzylpiperazine (IV) is converted to (III) by heating up to 170-250 C.
| 【1】 Boksay, I.J.E.; et al.; Synthesis and pharmacological activity of befuralline, a new antidepressnt compound. Arzneim-Forsch Drug Res 1978, 28, 19, Suppl. 2. |
| 【2】 Soeder, A.; et al. (Aventis Pharma AG); Cyclic diamine derivatives. DE 2157424; DE 2240665; ES 408565; FR 2160611; GB 1407854; US 4374990 . |
| 【3】 Unterhalt, B.; Befuraline Hydrochloride. Drugs Fut 1978, 3, 6, 426. |
| 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) | 39812 | 1-benzofuran-2-carbonyl chloride | 41717-28-6 | C9H5ClO2 | 详情 | 详情 |
| (II) | 28542 | N-Benzylpiperazine; 1-Benzylpiperazine | 2759-28-6 | C11H16N2 | 详情 | 详情 |
| (III) | 39813 | 1-benzofuran-2-yl(4-benzyl-1-piperazinyl)methanone | C20H20N2O2 | 详情 | 详情 | |
| (IV) | 39814 | 1-benzylpiperazin-4-ium 1-benzofuran-2-carboxylate | C20H22N2O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)This compound can be obtained in three different ways: 1) Condensation of pyridine-2-carboxylic acid (Ia, R = H), with 1-phenyl methylpiperazine (II) at 160 C. 2) Condensation of methyl pyridine-2-carboxylate (Ib, R = CH3) with 1-phenylmethylpiperazine (II) at 140 C. 3) Reaction of 1-phenylmethylpiperazine (II) with a mixed anhydride (III) formed from (Ia) and ethyl chloroformate (IV).
| 【1】 Budai, Z.; Zolyomi, G.; Synthesis of 14C and 3H specifically labelled 1-benzyl-4-picolinoylpiperazine. J Label Compd Radiopharm 1981, 18, 427-432. |
| 【2】 Budai, Z.; Mezei, T.; Lay, A.; A novel synthesis of pyridinecarboxylic acid piperazides. Acta Chim Acad Sci Hung 1980, 105, 241-246. |
| 【3】 Budai, Z.; Mezei, T.; Lay, A. (Egis Pharmaceuticals Ltd.); Preparation of pyridinecaboxylic acid piperazides. DE 2828888; GB 2001062; HU 175075 . |
| 【4】 Korosi, J.; et al. (Egis Pharmaceuticals Ltd.); Pyridine derivatives. DE 2215545; GB 1378964; HU 162396; JP 7644957 . |
| 【5】 Nogradi, M.; Piberaline. Drugs Fut 1984, 9, 1, 30. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (Ia) | 29950 | 2-pyridinecarboxylic acid；picolinic acid;Pyridine-2-carboxylic acid | 98-98-6 | C6H5NO2 | 详情 | 详情 |
| (Ib) | 29951 | methyl 2-pyridinecarboxylate | 2459-07-6 | C7H7NO2 | 详情 | 详情 |
| (II) | 28542 | N-Benzylpiperazine; 1-Benzylpiperazine | 2759-28-6 | C11H16N2 | 详情 | 详情 |
| (III) | 29952 | ethyl 2-oxo-2-(2-pyridinyl)acetate | C9H9NO3 | 详情 | 详情 | |
| (IV) | 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3
该中间体在本合成路线中的序号：(I)The condensation of N-benzylpiperazine (I) with ethyl isocyanate (II) in refluxing ether gives N-ethyl-4-benzyl-1-piperazinecarboxamide (III), which is debenzylated by hydrogenolysis with H2 over Pd/C in ethanol - HCl yielding N'-ethyl-1-piperazinecarboxarnide (IV). Finally, this compound is condensed with 1,1-bis(4-fluorophenyl)-4-chlorobutane (V) by means of NaHCO3 in refluxing ethanol.
| 【1】 Bjoerk, A.K.K.; Olsson, K.G.; Abramo, A.L.; Christensson, E.G.; DE 2941880 . |
| 【2】 Gluchowski, C.; Chiu, G.; Marzabadi, M.R.; Nagarathnam, D.; Lagu, B.; Noble, S.; Wetzel, J.; Deleon, J.E. (Synaptic Pharmaceutical Corp.); Selective melanin concentrating hormone-1 (MCH1) receptor antagonists and uses thereof. EP 1299362; WO 0206245 . |
| 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) | 28542 | N-Benzylpiperazine; 1-Benzylpiperazine | 2759-28-6 | C11H16N2 | 详情 | 详情 |
| (II) | 28738 | ethyl isocyanate | 109-90-0 | C3H5NO | 详情 | 详情 |
| (III) | 37048 | 4-benzyl-N-ethyl-1-piperazinecarboxamide | C14H21N3O | 详情 | 详情 | |
| (IV) | 37049 | N-ethyl-1-piperazinecarboxamide | C7H15N3O | 详情 | 详情 | |
| (V) | 37050 | 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene | 3312-04-7 | C16H15ClF2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XIII)The intermediate 5-fluoro-3-[3-(1-piperazinyl)propyl]-1H-indole (V) has been obtained as follows: a) The condensation of 5-fluoro-1H-indole (VIII) with acrylic acid (IX) by means of acetic anhydride gives 3-(1H-indol-5-yl)propionic acid (X), which is reduced with LiAlH4 to 3-(1H-indol-5-yl)-1-propanol (XI). The tosylation of (XI) with tosyl chloride yields the tosylate (XII), which is condensed with 1-benzylpiperazine (XIII) in refluxing butyl acetate affording 3-[3-(4-benzylpiperazin-1-yl)propyl]-5-fluoro-1H-indole (XIV). Finally, this compound is debenzylated by hydrogenation with H2 over Pd/C yielding the target intermediate (V). b) The tosylate intermediate (XII) can also be condensed with ethyl piperazine-1-carboxylate (XVII) in refluxing butyl acetate giving 4-[3-(5-fluoro-1H-indol-3-yl)propyl]piperazine-1-carboxylic acid ethyl ester (XVIII), which is then decarboxylated with NaOH to the target intermediate (V). The intermediate 3-(1H-indol-5-yl)-1-propanol (XI) can also be obtained by direct cyclization of 4-fluorophenylhydrazine (XV) with dihydropyran (XVI) in hot propyleneglycol.
| 【1】 Anderson, N.G.; et al.; Process development of 5-fluoro-3[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]propyl]-1H-indole dihydrochloride. Org Process Res Dev 1997, 1, 4, 300. |
| 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) | 32385 | 5-fluoro-3-[3-(1-piperazinyl)propyl]-1H-indole | C15H20FN3 | 详情 | 详情 | |
| (VIII) | 32388 | 5-Fluoroindole; 5-Fluoro-1H-indole | 399-52-0 | C8H6FN | 详情 | 详情 |
| (IX) | 19139 | acrylic acid | 79-10-7 | C3H4O2 | 详情 | 详情 |
| (X) | 32389 | 3-(5-fluoro-1H-indol-3-yl)propionic acid | C11H10FNO2 | 详情 | 详情 | |
| (XI) | 32390 | 3-(5-fluoro-1H-indol-3-yl)-1-propanol | C11H12FNO | 详情 | 详情 | |
| (XII) | 32391 | 3-(5-fluoro-1H-indol-3-yl)propyl 4-methylbenzenesulfonate | C18H18FNO3S | 详情 | 详情 | |
| (XIII) | 28542 | N-Benzylpiperazine; 1-Benzylpiperazine | 2759-28-6 | C11H16N2 | 详情 | 详情 |
| (XIV) | 32392 | 3-[3-(4-benzyl-1-piperazinyl)propyl]-5-fluoro-1H-indole | C22H26FN3 | 详情 | 详情 | |
| (XV) | 22135 | 1-(4-fluorophenyl)hydrazine | 371-14-2 | C6H7FN2 | 详情 | 详情 |
| (XVI) | 13684 | 3,4-Dihydro-2H-pyran;2,3-Dihydro-4H-pyran; 5,6-Dihydro-4H-pyran;Dihydropyran | 110-87-2 | C5H8O | 详情 | 详情 |
| (XVII) | 24694 | N-ethoxycarbonylpiperidine; Ethyl 1-piperazinecarboxylate; N-Ethoxycarbonyl piperazine; N-Carbethoxy piperazine | 120-43-4 | C7H14N2O2 | 详情 | 详情 |
| (XVIII) | 32393 | ethyl 4-[3-(5-fluoro-1H-indol-3-yl)propyl]-1-piperazinecarboxylate | C18H24FN3O2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(VIII)The reaction of isovanillin with hydroxylamine sulfate and NaOH in refluxing ethanol/water gives the corresponding oxime (II), which is reduced with Raney-Ni and NaOH in the same solvent yielding the benzylamine (III). The protection of the amino group of (III) with benzyloxycarbonyl chloride affords the carbamate (IV), which is condensed with ethyl bromoacetate (IV) by means of K2CO3 in refluxing 2-butanone to give the ester (VI). The hydrolysis of (VI) with NaOH in hot methanol/water yields the corresponding acid (VII), which is condensed with 1-benzylpiperazine (VIII) by means of ethyl chloroformate in THF to afford the piperazide (IX). The deprotection of the amino group of (IX) with H2 over Pd/C in hot ethanol gives the benzylamine (X), which is finally condensed with 4,5-dichloropyridazin-3(2H)-one (XI) by means of triethylamine in refluxing ethanol/water.
| 【1】 Tanikawa, K.; Saito, A.; Hirotsuka, M.; Shikada, K. (Nissan Chemical Industry, Ltd.); Pyridazinone derivs. with pharmaceutical activity. EP 0706517; JP 1996041033; US 5728702; US 5929074; WO 9501343 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 | |
| (I) | 18455 | 3-hydroxy-4-methoxybenzaldehyde; Isovanillin | 621-59-0 | C8H8O3 | 详情 | 详情 |
| (II) | 30957 | 2-methoxy-5-[(methylimino)methyl]phenol | C9H11NO2 | 详情 | 详情 | |
| (III) | 30958 | 5-(aminomethyl)-2-methoxyphenol | C8H11NO2 | 详情 | 详情 | |
| (IV) | 30959 | benzyl 3-hydroxy-4-methoxybenzylcarbamate | C16H17NO4 | 详情 | 详情 | |
| (V) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (VI) | 30960 | ethyl 2-[5-([[(benzyloxy)carbonyl]amino]methyl)-2-methoxyphenoxy]acetate | C20H23NO6 | 详情 | 详情 | |
| (VII) | 30961 | 2-[5-([[(benzyloxy)carbonyl]amino]methyl)-2-methoxyphenoxy]acetic acid | C18H19NO6 | 详情 | 详情 | |
| (VIII) | 28542 | N-Benzylpiperazine; 1-Benzylpiperazine | 2759-28-6 | C11H16N2 | 详情 | 详情 |
| (IX) | 30962 | benzyl 3-[2-(4-benzyl-1-piperazinyl)-2-oxoethoxy]-4-methoxybenzylcarbamate | C29H33N3O5 | 详情 | 详情 | |
| (X) | 30963 | 2-[5-(aminomethyl)-2-methoxyphenoxy]-1-(4-benzyl-1-piperazinyl)-1-ethanone | C21H27N3O3 | 详情 | 详情 | |
| (XI) | 24750 | Bis(isopropylamine)dichloro platinum complex | C6H18Cl2N2Pt | 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 title compound was prepared by condensation between 1-benzylpiperazine (I) and 5-chloro-2-methyl-4-nitroaniline (II) in the presence of K2CO3 in either refluxing ethanol or, with a higher yield, in DMF at 120 C. Treatment with HCl in isopropanol furnished the corresponding dihydrochloride salt.
| 【1】 Rátzné Simonek, I.; Bózsing, D.; Jakóczi, I.; Koványiné Lax, G.; Blaskó, G.; Simig, G.; Gacsályi, I.; Schmidt, E.; Miklósné Kovács, A.; Szirtné Kiszelly, E.; Szénási, G.; Gyertyán, I.; Egyed, A.; Tihanyi, K. (Egis Pharmaceuticals Ltd.); Novel piperazine or homopiperazine derivs., pharmaceutical compsns. containing the same and a process for their preparation. WO 9744334 . |
合成路线7
该中间体在本合成路线中的序号：(VI)Protection of 3-hydroxybenzaldehyde (I) with methoxymethyl chloride afforded the corresponding methoxymethyl ether (II). Subsequent addition of 4-tert-butylphenylmagnesium bromide (III) produced the diarylcarbinol (IV), which was converted to chloride (V) by means of CCl4 and PPh3. Condensation of (V) with 1-benzylpiperazine (VI) yielded the disubstituted piperazine (VII). The methoxymethyl ether of (VII) was finally deprotected with aqueous HCl to provide the title compound.
| 【1】 Liao, S.; Alfaro-Lopez, J.; Shenderovich, M.D.; Hosohata, K.; Lin, J.; Li, X.; Stropova, D.; Davis, P.; Jernigan, K.A.; Porreca, F.; Yamamura, H.I.; Hruby, V.J.; De novo design, synthesis, and biological activities of high-affinity and selective non-peptide agonists of the delta-opioid receptor. J Med Chem 1998, 41, 24, 4767. |
| 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) | 28537 | 3-hydroxybenzaldehyde | 100-83-4 | C7H6O2 | 详情 | 详情 |
| (II) | 28538 | 3-(methoxymethoxy)benzaldehyde | C9H10O3 | 详情 | 详情 | |
| (III) | 28539 | bromo[4-(tert-butyl)phenyl]magnesium | C10H13BrMg | 详情 | 详情 | |
| (IV) | 28540 | [4-(tert-butyl)phenyl][3-(methoxymethoxy)phenyl]methanol | C19H24O3 | 详情 | 详情 | |
| (V) | 28541 | 1-[[4-(tert-butyl)phenyl](chloro)methyl]-3-(methoxymethoxy)benzene | C19H23ClO2 | 详情 | 详情 | |
| (VI) | 28542 | N-Benzylpiperazine; 1-Benzylpiperazine | 2759-28-6 | C11H16N2 | 详情 | 详情 |
| (VII) | 28543 | (3-[(4-benzyl-1-piperazinyl)[4-(tert-butyl)phenyl]methyl]phenoxy)methyl methyl ether | C30H38N2O2 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(III)4-Fluoro-3-trifluoromethylbenzoic acid (I) is esterified employing MeOH and SOCl2 to afford the methyl ester (II). Displacement of the 4-fluoride of (II) with N-benzylpiperazine (III) in hot DMSO yields the piperazinyl benzoate (IV). The N-benzyl group of (IV) is then removed by hydrogenolysis over Pd/C to yield the deprotected piperazine (V), which is further coupled with 2-pyrrolecarboxylic acid (VI) by means of CDI producing amide (VII). Finally, displacement of the methyl ester of (VII) with guanidine (VIII) gives rise to the target acyl guanidine, which is converted to the corresponding mesylate salt
| 【1】 Roos, O.; Eickmeier, C.; Blech, S.-M.; Búrger, E. (Boehringer Ingelheim Pharma GmbH & Co. KG); Benzoylguanidine derivs. with advantageous properties, method for producing them and their use in the production of medicaments. DE 19843489; JP 2002538077; US 6323207; WO 0017176 . |
| 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) | 62343 | 4-fluoro-3-(trifluoromethyl)benzoic acid | C8H4F4O2 | 详情 | 详情 | |
| (II) | 62344 | methyl 4-fluoro-3-(trifluoromethyl)benzoate | C9H6F4O2 | 详情 | 详情 | |
| (III) | 28542 | N-Benzylpiperazine; 1-Benzylpiperazine | 2759-28-6 | C11H16N2 | 详情 | 详情 |
| (IV) | 62345 | methyl 4-(4-benzyl-1-piperazinyl)-3-(trifluoromethyl)benzoate | C20H21F3N2O2 | 详情 | 详情 | |
| (V) | 62346 | methyl 4-(1-piperazinyl)-3-(trifluoromethyl)benzoate | C13H15F3N2O2 | 详情 | 详情 | |
| (VI) | 31796 | Pyrrole-2-carboxylic acid; 1H-pyrrole-2-carboxylic acid | 634-97-9 | C5H5NO2 | 详情 | 详情 |
| (VII) | 62347 | methyl 4-[4-(1H-pyrrol-2-ylcarbonyl)-1-piperazinyl]-3-(trifluoromethyl)benzoate | C18H18F3N3O3 | 详情 | 详情 | |
| (VIII) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(I)Acylation of N-benzylpiperazine (I) with propionyl chloride afforded amide (II). Hydrogenolysis of the N-benzyl protecting group of (II) over Pd/C then gave N-propionyl piperazine (III), which was finally condensed with benzoyl chloride to yield the title diamide.
| 【1】 Galeotti, N.; Gualtiere, F.; Mannetti, D.; Ghelardini, C.; Romanelli, M.N.; Bartolini, A.; Dei, S.; Teodori, E.; Molecular simplification of 1,4-diazabicyclo[4.3.0]nonan-9-ones gives piperazine derivatives that maintain high nootropic activity. J Med Chem 2000, 43, 23, 4499. |
| 【2】 Bellucci, C.; Ghelardini, C.; Dei, S.; Bartolini, A.; Galeotti, N.; Romanelli, M.N.; Gualtiere, F.; Manetti, D.; Scapecchi, S.; Teodori, E.; 1,4-Diazabicyclo[4.3.0]nonan-9-ones and 1,4-diamidopiperazines as new classes of highly potent nootropic drugs. 16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000, Abst PB-119. |
合成路线10
该中间体在本合成路线中的序号：(VI)Alkylation of 1-benzylpiperazine (VI) with 2-(4-fluorophenoxy)ethyl bromide (VII) produced the dialkylated piperazine (VIII). The benzyl protecting group of (VIII) was then removed hydrogenolysis in the presence of Pearlman's catalyst to furnish (IX). The title compound was then obtained by condensation of piperazine (IX) with mesylate (V) or, alternatively, by reductive alkylation of (IX) with aldehyde (X) in the presence of sodium triacetoxyborohydride.
| 【1】 Yamamoto, N.; et al.; Discovery of a potent neuron-selective calcium channel blocker: Structure-activity relationships and neuroprotective effects of novel piperazine derivatives. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 51. |
| 【2】 Niidome, T.; Norimine, Y.; Teramoto, T.; Kawano, K.; Kimura, T.; Iimura, Y.; Yamamoto, N.; Suzuki, Y.; Ito, K.; Hatakeyama, S.; Nagato, S.; Komatsu, M. (Eisai Co., Ltd.); N,N-Substd. cyclic amine derivs.. EP 1099692; JP 2000169462; WO 0005210 . |
| 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) | 49823 | 4-cyano-5-methyl-4-phenylhexyl methanesulfonate | C15H21NO3S | 详情 | 详情 | |
| (VI) | 28542 | N-Benzylpiperazine; 1-Benzylpiperazine | 2759-28-6 | C11H16N2 | 详情 | 详情 |
| (VII) | 20830 | 1-(2-bromoethoxy)-4-fluorobenzene; 2-bromoethyl 4-fluorophenyl ether | 332-48-9 | C8H8BrFO | 详情 | 详情 |
| (VIII) | 49824 | 1-benzyl-4-[2-(4-fluorophenoxy)ethyl]piperazine; 2-(4-benzyl-1-piperazinyl)ethyl 4-fluorophenyl ether | C19H23FN2O | 详情 | 详情 | |
| (IX) | 49825 | 4-fluorophenyl 2-(1-piperazinyl)ethyl ether; 1-[2-(4-fluorophenoxy)ethyl]piperazine | C12H17FN2O | 详情 | 详情 | |
| (X) | 49826 | 2-isopropyl-5-oxo-2-phenylpentanenitrile | C14H17NO | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(VI)In a further procedure, 1-benzylpiperazine (VI) was alkylated with mesylate (V) to yield adduct (XI). Catalytic hydrogenolysis of the benzyl group of (XI) afforded piperazine (XII), which was finally alkylated with 2-(4-fluorophenoxy)ethyl bromide (VII) in the presence of triethylamine.
| 【1】 Yamamoto, N.; et al.; Discovery of a potent neuron-selective calcium channel blocker: Structure-activity relationships and neuroprotective effects of novel piperazine derivatives. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 51. |
| 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) | 49823 | 4-cyano-5-methyl-4-phenylhexyl methanesulfonate | C15H21NO3S | 详情 | 详情 | |
| (VI) | 28542 | N-Benzylpiperazine; 1-Benzylpiperazine | 2759-28-6 | C11H16N2 | 详情 | 详情 |
| (VII) | 20830 | 1-(2-bromoethoxy)-4-fluorobenzene; 2-bromoethyl 4-fluorophenyl ether | 332-48-9 | C8H8BrFO | 详情 | 详情 |
| (XI) | 49827 | 5-(4-benzyl-1-piperazinyl)-2-isopropyl-2-phenylpentanenitrile | C25H33N3 | 详情 | 详情 | |
| (XII) | 49828 | 2-isopropyl-2-phenyl-5-(1-piperazinyl)pentanenitrile | C18H27N3 | 详情 | 详情 |
合成路线12
该中间体在本合成路线中的序号：(IV)2-Mercapto-4-quinazolone (I) is treated with ethyl iodide (II) in the presence of sodium ethoxide to yield 2-ethylthio-4-quinazolone (III). Reaction of (III) with N-benzylpiperazine (IV) to give (V) and followed by catalytic debenzylation with H2 over Pd/C in glacial acetic acid affords Centpiperalone.
| 【1】 Gupta, C.M.; Muscimol analogs. II. Synthesis of some bicyclic 3-isoxazolol zwitterions. Med Chem 1968, 11, 3, 392. |
| 【2】 Arya, V.P.; Centpiperalone. Drugs Fut 1979, 4, 8, 557. |
| 【3】 Gupta, C.M.; et al.; Resveratrol regulates IGF-II in MCF-7 human breast cancer cells. Ind J Chem 1971, 9, 3, 201. |
| 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) | 61384 | 2-Mercapto-4(3H)-quinazolinone 2-Thio-4(3H)-quinazolinone; 2-Mercapto-4(3H)-quinazolinone 2-Thio-4(3H)-quinazolinone | 13906-09-7 | C8H6N2OS | 详情 | 详情 |
| (II) | 10925 | Iodoethane;ethyl iod | 75-03-6 | C2H5I | 详情 | 详情 |
| (III) | 61385 | 2-(ethylsulfanyl)-4(3H)-quinazolinone | C10H10N2OS | 详情 | 详情 | |
| (IV) | 28542 | N-Benzylpiperazine; 1-Benzylpiperazine | 2759-28-6 | C11H16N2 | 详情 | 详情 |
| (V) | 61386 | 2-(4-benzyl-1-piperazinyl)-4(3H)-quinazolinone | C19H20N4O | 详情 | 详情 |