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【结 构 式】 
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【分子编号】25248 【品名】N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine 【CA登记号】109-55-7 |
【 分 子 式 】C5H14N2 【 分 子 量 】102.17964 【元素组成】C 58.77% H 13.81% N 27.42% |
合成路线1
该中间体在本合成路线中的序号：(X)The condensation of diethylgermanium dihydride (I) with methyl acrylate (II) gives diethyldi-(beta-carbomethoxyethyl)germane (III), which is cyclized by treatment with potassium tert-butoxide in refluxing toluene yielding carbomethoxy-4,4-diethyl-4-germacyclohexanone (IV). The decarboxylative hydrolysis of (IV) with refluxing 20% aqueous H2SO4 affords 4,4-diethyl-4-germacyclohexanone (V), which is condensed with ethyl cyanoacetate (VI) by means of ammonium acetate acetic acid in refluxing benzene giving ethyl alpha-cyano-alpha-(4,4-diethyl-4-germacyclohexylidene)acetate (VII). The treatment of (VII) with KCN in ethanol-water, and then with refluxing aqueous HCl yields 4,4-diethyl-4-germacyclohexane-1-carboxy-1-acetic acid (VIII), which is then converted into its cyclic anhydride (IX) by reaction with refluxing acetic anhydride. The reaction of (IX) with 3-dimethylaminopropylamine (X) at 180 C gives N-(3-dimethylaminopropyl)-2-aza-8,8-diethyl-8-germaspiro[4.5]decane-1,3-dione (XI), which is finally reduced with LiAlH4 in benzene-ether.
| 【1】 Rice, L.M.; US 3825546 . |
| 【2】 Rice, L.M.; et al.; Spirans. XXII. Synthesis of 4,4-dialkyl-4-germacyclohexanone and 8,8-dialkyl-8-germaazaspiro[4,5]decanes. J Heterocycl Chem 1974, 11, 6, 1041-47. |
| 【3】 Castaner, J.; Spirogermanium Hydrochloride. Drugs Fut 1980, 5, 3, 149. |
| 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) | 39022 | diethyl-lambda(2)-germane | C4H12Ge | 详情 | 详情 | |
| (II) | 14156 | methyl acrylate | 96-33-3 | C4H6O2 | 详情 | 详情 |
| (III) | 39023 | methyl 3-[diethyl(3-methoxy-3-oxopropyl)germyl]propanoate | C12H24GeO4 | 详情 | 详情 | |
| (IV) | 39024 | methyl 1,1-diethyl-4-oxo-3-germinanecarboxylate | C11H20GeO3 | 详情 | 详情 | |
| (V) | 39025 | 1,1-diethyl-4-germinanone | C9H18GeO | 详情 | 详情 | |
| (VI) | 11877 | Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate | 105-56-6 | C5H7NO2 | 详情 | 详情 |
| (VII) | 39026 | ethyl 2-cyano-2-(1,1-diethyl-4-germinanylidene)acetate | C14H23GeNO2 | 详情 | 详情 | |
| (VIII) | 39027 | 4-(carboxymethyl)-1,1-diethyl-4-germinanecarboxylic acid | C12H22GeO4 | 详情 | 详情 | |
| (IX) | 39028 | 8,8-diethyl-2-oxa-8-germaspiro[4.5]decane-1,3-dione | C12H20GeO3 | 详情 | 详情 | |
| (X) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |
| (XI) | 39029 | 2-[3-(dimethylamino)propyl]-8,8-diethyl-2-aza-8-germaspiro[4.5]decane-1,3-dione | C17H32GeN2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XII)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3
该中间体在本合成路线中的序号：(III)BI 397 is the 3-(dimethylamino)-1-propylamide at the peptide-carboxy group of the natural glycopeptide A-40,926. BI 397 is prepared from A-40,926 following a three-step procedure which consists of: 1) selective methyl esterification of the N-acylaminoglucuronic acid function, 2) amidation of the peptide-carboxy group and 3) saponification of the sugar methyl ester. Steps 2 and 3 are performed in one-pot. Step 1): Reaction of A-40,926 (A) (I) in methanol in the presence of H2SO4 at 0-5 C for 24 h gives the monomethyl ester (MA) (II) at the sugar-carboxy group (80% yield). Step 2): Amidation at the peptide-carboxy group is carried out by reaction of MA (II) with 3-(dimethylamino)-1-propylamine (DMEPA) (III) in DMSO in the presence of PyBOP to obtain the methyl ester (MA-A-1) (IV) of BI 397; this compound is not isolated. Step 3): Hydrolysis of MA-A-1 (IV) in the above DMSO solution with 15% NAOH gives BI 397 (A-A-1, 63% yield from MA).
| 【1】 Scotti, R.; Kurz, M.; Andreini, B.P.; Goldstein, B.P.; Denaro, M.; Ferrari, P.; Ciabatti, R.; Malabarba, A.; New semisynthetic glycopepetides MDL 63,246 and MDL 63,042, and other amide derivatives of antibiotic A-40,926 active against glycopeptide-resistant VanA enterococci. J Antibiot 1995, 48, 8, 869. |
| 【2】 Donadio, S.; Malabarba, A.; BI 397. Drugs Fut 1999, 24, 8, 839. |
| 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) | 25999 | (3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-38-carboxylic acid; (3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-38-carboxylic acid | C83H88Cl2N8O29 | 详情 | 详情 | |
| (II) | 26000 | (3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid methyl ester]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-38-carboxylic acid; (3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid methyl ester]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-38-carboxylic acid | C84H90Cl2N8O29 | 详情 | 详情 | |
| (III) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |
| (IV) | 26001 | (3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid methyl ester]-N-[3-(dimethylamino)propyl]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-38-carboxamide; (3S,15R,18R,34R,35S,38S,48R,50aR)-5,31-Dichloro-56-[2-deoxy-3-(10-methylundecanamido)-beta-D-glucopyranosyloxyuronic acid methyl ester]-N-[3-(dimethylamino)propyl]-6,11,34,40,44-pentahydroxy-42-(alpha-D-mannopyranosyloxy)-15-(methylamino)-2,16,36,50,51,59-hexaoxo-2,3,16,17,18,19,35,36,37,38,48,49,50,50a-tetradecahydro-1H,15H,34H-20,23:30,33-dietheno-3,18:35,48-bis(iminomethano)-4,8:10,14:25,28:43,47-tetrametheno-[1,14,6,28]dioxadiazacyclooctacosino[4,5-m][10,2,16]benzoxadiazacyclote | C89H102Cl2N10O28 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(VIII)Condensation of 4,5-dichloro-1,2-phenylenediamine (I) with 1-phenyl-1,2-propanedione (II) in boiling AcOH provided quinoxaline (III). Subsequent reaction of (III) with ethyl bromopyruvate (IV) led to the pyrroloquinoxaline (V). After reduction of the ester group of (V) to alcohol (VI) with LiAlH4, further oxidation with MnO2 produced aldehyde (VII). This was condensed with boiling 3-(dimethylamino)propylamine (VIII), and the resulting imine (IX) was finally reduced to the target amine with NaBH4 in MeOH. The title compound was finally converted to the dioxalate salt upon treatment with oxalic acid in isopropanol.
| 【1】 Guillon, J.; Rault, S.; Kervran, A.; Renard, P.; Manechez, D.; Pfeiffer, B.; Dallemagne, P.; Synthesis of new pyrrolo[1,2-a]quinoxalines: Potential non-peptide glucagon receptor antagonists. Eur J Med Chem 1998, 33, 4, 293. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 15713 | Oxalic acid | 144-62-7 | C2H2O4 | 详情 | 详情 | |
| (I) | 18003 | 4,5-dichloro-1,2-benzenediamine; 4,5-Dichloro-o-phenylenediamine; 2-amino-4,5-dichlorophenylamine | 5348-42-5 | C6H6Cl2N2 | 详情 | 详情 |
| (II) | 31481 | 1-phenyl-1,2-propanedione | 579-07-7 | C9H8O2 | 详情 | 详情 |
| (III) | 31482 | 6,7-dichloro-2-methyl-3-phenylquinoxaline | C15H10Cl2N2 | 详情 | 详情 | |
| (IV) | 25183 | ethyl 3-bromo-2-oxopropanoate;ethyl 3-bromopyruvate;Bromopyruvic acid ethyl ester;ethyl 3-bromopyruvate;ethyl bromopyruvate | 70-23-5 | C5H7BrO3 | 详情 | 详情 |
| (V) | 31483 | ethyl 7,8-dichloro-4-phenylpyrrolo[1,2-a]quinoxaline-2-carboxylate | C20H14Cl2N2O2 | 详情 | 详情 | |
| (VI) | 31484 | (7,8-dichloro-4-phenylpyrrolo[1,2-a]quinoxalin-2-yl)methanol | C18H12Cl2N2O | 详情 | 详情 | |
| (VII) | 31486 | 7,8-dichloro-4-phenylpyrrolo[1,2-a]quinoxaline-2-carbaldehyde | C18H10Cl2N2O | 详情 | 详情 | |
| (VIII) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |
| (IX) | 31485 | N(1)-[(E)-(7,8-dichloro-4-phenylpyrrolo[1,2-a]quinoxalin-2-yl)methylidene]-N(3),N(3)-dimethyl-1,3-propanediamine; N-[(E)-(7,8-dichloro-4-phenylpyrrolo[1,2-a]quinoxalin-2-yl)methylidene]-N-[3-(dimethylamino)propyl]amine | C23H22Cl2N4 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(IX)The N-arylpyrrole (III) was prepared by the Clauson-Kaas reaction of 2-nitroaniline (I) with 2,5-dimethoxytetrahydrofuran (II) in AcOH under microwave irradiation. Subsequent reduction of the nitro group of (III) using BiCl3 and NaBH4 provided aniline (IV), which was condensed with cinnamoyl chloride (V) in the presence of pyridine to give the corresponding amide (VI). Cyclization of (VI) using POCl3 and pyridine produced the pyrroloquinoxaline (VII), and further Vilsmeier-Haack formylation gave aldehyde (VIII). This was condensed with boiling 3-(dimethylamino)propylamine (IX), and the resulting imine (X) was finally reduced to the target amine with NaBH4 in MeOH. The title compound was finally converted to the trioxalate salt upon treatment with oxalic acid in isopropanol.
| 【1】 Guillon, J.; Rault, S.; Kervran, A.; Renard, P.; Manechez, D.; Pfeiffer, B.; Dallemagne, P.; Synthesis of new pyrrolo[1,2-a]quinoxalines: Potential non-peptide glucagon receptor antagonists. Eur J Med Chem 1998, 33, 4, 293. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 15713 | Oxalic acid | 144-62-7 | C2H2O4 | 详情 | 详情 | |
| (I) | 11608 | o-Nitroaniline; 2-Nitroaniline; 2-Nitrophenylamine | 88-74-4 | C6H6N2O2 | 详情 | 详情 |
| (II) | 12132 | 2,5-Dimethoxytetrahydrofuran; 5-Methoxytetrahydro-2-furanyl methyl ether | 696-59-3 | C6H12O3 | 详情 | 详情 |
| (III) | 31487 | 1-(2-nitrophenyl)-1H-pyrrole | 33265-60-0 | C10H8N2O2 | 详情 | 详情 |
| (IV) | 31488 | 2-(1H-pyrrol-1-yl)aniline; 2-(1H-pyrrol-1-yl)phenylamine | 6025-60-1 | C10H10N2 | 详情 | 详情 |
| (V) | 11303 | (E)-3-Phenyl-2-propenoyl chloride; 3-Phenyl-2-propenoyl chloride | 102-92-1 | C9H7ClO | 详情 | 详情 |
| (VI) | 31489 | (E)-3-phenyl-N-[2-(1H-pyrrol-1-yl)phenyl]-2-propenamide | C19H16N2O | 详情 | 详情 | |
| (VII) | 31490 | 4-[(E)-2-phenylethenyl]pyrrolo[1,2-a]quinoxaline | C19H14N2 | 详情 | 详情 | |
| (VIII) | 31491 | 4-[(E)-2-phenylethenyl]pyrrolo[1,2-a]quinoxaline-1-carbaldehyde | C20H14N2O | 详情 | 详情 | |
| (IX) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |
| (X) | 31492 | N-[3-(dimethylamino)propyl]-N-((E)-[4-[(E)-2-phenylethenyl]pyrrolo[1,2-a]quinoxalin-1-yl]methylidene)amine; N(1),N(1)-dimethyl-N(3)-((E)-[4-[(E)-2-phenylethenyl]pyrrolo[1,2-a]quinoxalin-1-yl]methylidene)-1,3-propanediamine | C25H26N4 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(XII)Alkylation of imidazole (I) with 1,7-dibromoheptane (II) by means of potassium (metal) in refluxing THF furnishes N,N'-bis-(1-imidazolyl)heptane (III), which is treated with trichloroacetyl chloride (IV) in CH2Cl2 to provide derivative (V). Nitration of (V) by means of nitric acid/sulfuric acid in Ac2O/CH2Cl2 yields compound (VI), which is then converted into intermediate (VIII) by coupling in DMF/THF with substituted pyrrole (VII). In turn, (VII) can be obtained as follows: Treatment of N-methylpyrrole (IX) with trichloroacetyl chloride (IV) in CH2Cl2 affords derivative (X), which is nitrated to yield compound (XI) in the same conditions as for nitration of (V). The last step involves coupling of (XI) with 3-(dimethylamino)propylamine (XII), followed by reduction of the nitro moiety by hydrogenation over Pd/C in DMF/MeOH. Finally, the target product can be obtained by first hydrogenation of intermediate (VIII) over Pd/C in DMF/MeOH, followed by reaction with DCC and HOBt in DMF to allow coupling with carboxylic acid (XIV), which can be obtained by saponification of ethyl ester (XIII) in EtOH.
| 【1】 Sharma, S.K.; et al.; Design and synthesis of novel thiazole-containing cross-linked polyamides related to tha antiviral antibiotic distamycin. J Org Chem 2000, 65, 4, 1102. |
| 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) | 10255 | Imidazole; 1H-Imidazole | 288-32-4 | C3H4N2 | 详情 | 详情 |
| (II) | 47013 | 1,7-dibromoheptane | 4549-31-9 | C7H14Br2 | 详情 | 详情 |
| (III) | 47014 | 1-[7-(1H-imidazol-1-yl)heptyl]-1H-imidazole | C13H20N4 | 详情 | 详情 | |
| (IV) | 47015 | 2,2,2-trichloroacetyl chloride | 76-02-8 | C2Cl4O | 详情 | 详情 |
| (V) | 47016 | 2,2,2-trichloro-1-(1-[7-[2-(2,2,2-trichloroacetyl)-1H-imidazol-1-yl]heptyl]-1H-imidazol-2-yl)-1-ethanone | C17H18Cl6N4O2 | 详情 | 详情 | |
| (VI) | 47017 | 2,2,2-trichloro-1-(4-nitro-1-[7-[4-nitro-2-(2,2,2-trichloroacetyl)-1H-imidazol-1-yl]heptyl]-1H-imidazol-2-yl)-1-ethanone | C17H16Cl6N6O6 | 详情 | 详情 | |
| (VII) | 47018 | 4-amino-N-[3-(dimethylamino)propyl]-1-methyl-1H-pyrrole-2-carboxamide | C11H20N4O | 详情 | 详情 | |
| (VIII) | 47019 | N-[5-([[3-(dimethylamino)propyl]amino]carbonyl)-1-methyl-1H-pyrrol-3-yl]-1-[7-[2-([[5-([[3-(dimethylamino)propyl]amino]carbonyl)-1-methyl-1H-pyrrol-3-yl]amino]carbonyl)-4-nitro-1H-imidazol-1-yl]heptyl]-4-nitro-1H-imidazole-2-carboxamide | C37H54N14O8 | 详情 | 详情 | |
| (IX) | 11285 | 1-Methyl-1H-pyrrole; Methylpyrrole | 96-54-8 | C5H7N | 详情 | 详情 |
| (X) | 47020 | 2,2,2-trichloro-1-(1-methyl-1H-pyrrol-2-yl)-1-ethanone | C7H6Cl3NO | 详情 | 详情 | |
| (XI) | 47021 | 2,2,2-trichloro-1-(1-methyl-4-nitro-1H-pyrrol-2-yl)-1-ethanone | C7H5Cl3N2O3 | 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 |
| (XIII) | 47022 | ethyl 2-amino-4-methylthiazole-5-carboxylate; ethyl 2-amino-4-methyl-1,3-thiazole-5-carboxylate | 7210-76-6 | C7H10N2O2S | 详情 | 详情 |
| (XIV) | 47023 | 2-amino-4-methyl-1,3-thiazole-5-carboxylic acid | C5H6N2O2S | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(II)The title compound was prepared starting from dibenzo[b,j](1,7)phenanthroline-2,10-dicarboxaldehyde (I). Condensation of dialdehyde (I) with 3-(dimethylamino)propylamine (II) produced the intermediate diimine (III), which was then reduced to the corresponding amine by using NaBH4 in MeOH.
| 【1】 Lacroix, L.; Mergny, J.-L.; Teulade-Frchou, M.-P.; et al.; Telomerase inhibitors based on quadruplex ligands selected by a fluorescence assay. Proc Natl Acad Sci USA 2001, 98, 6, 3062. |
| 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) | 50158 | dibenzo[b,j][1,7]phenanthroline-2,10-dicarbaldehyde | C22H12N2O2 | 详情 | 详情 | |
| (II) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |
| (III) | 50159 | N(1)-[(E)-[10-([[3-(dimethylamino)propyl]imino]methyl)dibenzo[b,j][1,7]phenanthrolin-2-yl]methylidene]-N(3),N(3)-dimethyl-1,3-propanediamine; N-[3-(dimethylamino)propyl]-N-[(E)-[10-([[3-(dimethylamino)propyl]imino]methyl)dibenzo[b,j][1,7]phenanthrolin-2-yl]methylidene]amine | C32H36N6 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(II)Alkylation of N,N-dimethyl-1,3-propanediamine (II) with ethyl bromoacetate (I) afforded the diamino ester (III). Basic hydrolysis of (III) and subsequent nitrosation of the resulting diamino acid (IV) yielded the nitrosamine (V). Cyclization of (V) in hot acetic anhydride as the dehydrating agent gave rise to sydnone (VI). Lithiation of (VI), followed by condensation with aldehyde (VII), produced adduct (VIII) as an inseparable mixture of diastereomers. The hydroxyl group of (VIII) was then protected as the methyl ether (IX) by alkylation with iodomethane and NaH. The azomethyne intermediate, generated by ejection of CO2 from (IX) upon heating in xylene, underwent an intramolecular 1,3-dipolar cycloaddition with the olefin double bond to furnish the indazole derivative (X). Finally, the target compound was obtained by aromatization of (X) under acidic conditions in the presence of platinum catalyst.
| 【1】 Yeu, J.P.; et al.; An expedient synthesis of 1-[3-(dimethylamino)propyl]-5-methyl-3-phenyl-1H-indazole (FS-32) - An antidepressant. Synthesis 2001, 12, 1775. |
| 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) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (II) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |
| (III) | 50245 | ethyl 2-[[3-(dimethylamino)propyl]amino]acetate | C9H20N2O2 | 详情 | 详情 | |
| (IV) | 50246 | 2-[[3-(dimethylamino)propyl]amino]acetic acid | C7H16N2O2 | 详情 | 详情 | |
| (V) | 50247 | C7H15N3O3 | 详情 | 详情 | ||
| (VI) | 50248 | 3-[3-(dimethylamino)propyl]-1,2,3-oxadiazol-3-ium-5-olate | C7H13N3O2 | 详情 | 详情 | |
| (VII) | 50249 | (E)-3-methyl-6-phenyl-5-hexenal | C13H16O | 详情 | 详情 | |
| (VIII) | 50250 | 3-[3-(dimethylamino)propyl]-4-[(E)-1-hydroxy-3-methyl-6-phenyl-5-hexenyl]-1,2,3-oxadiazol-3-ium-5-olate | C20H29N3O3 | 详情 | 详情 | |
| (IX) | 50251 | 3-[3-(dimethylamino)propyl]-4-[(E)-1-methoxy-3-methyl-6-phenyl-5-hexenyl]-1,2,3-oxadiazol-3-ium-5-olate | C21H31N3O3 | 详情 | 详情 | |
| (X) | 50252 | 3-(7-methoxy-5-methyl-3-phenyl-4,5,6,7-tetrahydro-1H-indazol-1-yl)-N,N-dimethyl-1-propanamine; N-[3-(7-methoxy-5-methyl-3-phenyl-4,5,6,7-tetrahydro-1H-indazol-1-yl)propyl]-N,N-dimethylamine | C20H29N3O | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(VIII)4-Chloroanthranilic acid (I) is acylated by butyryl chloride (II) in DMF to produce amide (III). This is then cyclized to the benzoxazinone (IV) upon heating with acetic anhydride. Condensation of (IV) with benzylamine (V) in refluxing chloroform, followed by treatment with NaOH in hot ethyleneglycol, gives rise to the quinazolinone (VI). Subsequent benzylic bromination of (VI) at the propyl side chain produces (VII). The bromide group of (VII) is then displaced with N,N-dimethyl-1,3-propanediamine (VIII) to furnish (IX). Finally, amine (IX) is acylated by 4-bromobenzoyl chloride (X) to afford the corresponding benzamide.
| 【1】 Chabala, J.C.; Morgans, D.J. Jr.; Feng, B.; Finer, J.T.; Bergnes, G.; Smith, W.W. (Cytokinetics, Inc.); Methods and compsns. utilizing quinazolinones. WO 0198278 . |
| 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) | 52504 | 4-Chloro-2-aminobenzoic acid; 2-Amino-4-chlorobenzoic acid; 2-Carboxy-5-chloroaniline; 3-Amino-4-carboxy-1-chlorobenzene; 4-Chloroanthranilic acid | 89-77-0 | C7H6ClNO2 | 详情 | 详情 |
| (II) | 10792 | Butanoyl chloride; Butyryl chloride | 141-75-3 | C4H7ClO | 详情 | 详情 |
| (III) | 58445 | 2-(butyrylamino)-4-chlorobenzoic acid | C11H12ClNO3 | 详情 | 详情 | |
| (IV) | 58446 | 7-chloro-2-propyl-4H-3,1-benzoxazin-4-one | C11H10ClNO2 | 详情 | 详情 | |
| (V) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (VI) | 58447 | 3-benzyl-7-chloro-2-propyl-4(3H)-quinazolinone | C18H17ClN2O | 详情 | 详情 | |
| (VII) | 58448 | 3-benzyl-2-(1-bromopropyl)-7-chloro-4(3H)-quinazolinone | C18H16BrClN2O | 详情 | 详情 | |
| (VIII) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |
| (IX) | 58449 | 3-benzyl-7-chloro-2-(1-{[3-(dimethylamino)propyl]amino}propyl)-4(3H)-quinazolinone | C23H29ClN4O | 详情 | 详情 | |
| (X) | 45960 | 4-bromobenzoyl chloride | 586-75-4 | C7H4BrClO | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(XIII)The tripyrrolyl acid (XII) is coupled with N,N-dimethyl-1,3-propanediamine (XIII) to afford amide (XIV). After acidic Boc group cleavage in (XIV), the resultant amino compound (XV) is acylated by 4,5-dichloroisothiazole-3-carboxylic acid (XVI) to furnish the tetra-heterocyclic amide (XVII). Finally, selective displacement of the 5-chloro group of (XVII) with 1,4-butanediamine (XVIII) gives rise to the title compound.
| 【1】 Ge, Y.; Taylor, M.J.; Baird, E.E.; Moser, H.E.; Burli, R.W. (GeneSoft, Inc.); Charged cpds. comprising a nucleic acid binding moiety and uses therefor. JP 2003529609; WO 0174898 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 53515 | 4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid | n/a | C23H28N6O6 | 详情 | 详情 |
| (XIII) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |
| (XIV) | 58476 | tert-butyl 5-({[5-({[5-({[3-(dimethylamino)propyl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-ylcarbamate | C28H40N8O5 | 详情 | 详情 | |
| (XV) | 58477 | 4-{[(4-{[(4-amino-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-N-[3-(dimethylamino)propyl]-1-methyl-1H-pyrrole-2-carboxamide | C23H32N8O3 | 详情 | 详情 | |
| (XVI) | 53577 | ((3aR,4R,6R,6aS)-2,2-dimethyl-6-{6-[(3R)tetrahydro-3-furanylamino]-9H-purin-9-yl}tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl methylcarbamate | n/a | C19H26N6O6 | 详情 | 详情 |
| (XVII) | 58478 | 4,5-dichloro-N-[5-({[5-({[5-({[3-(dimethylamino)propyl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]-3-isothiazolecarboxamide | C27H31Cl2N9O4S | 详情 | 详情 | |
| (XVIII) | 42070 | 1,4-butanediamine; 4-aminobutylamine | 110-60-1 | C4H12N2 | 详情 | 详情 |