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【结 构 式】

【分子编号】10015

【品名】1-Hydrazinecarboximidamide; Hydrazinecarboximidamide

【CA登记号】79-17-4

【 分 子 式 】CH6N4

【 分 子 量 】74.0856

【元素组成】C 16.21% H 8.16% N 75.62%
与该中间体有关的原料药合成路线共 16 条
合成路线1合成路线2合成路线3合成路线4合成路线5合成路线6合成路线7合成路线8合成路线9合成路线10合成路线11合成路线12合成路线13合成路线14合成路线15合成路线16

合成路线1

该中间体在本合成路线中的序号：(V)

The synthesis of [14C]-mitoguazone has been reported: The methylation of [14C]-labeled potassium acetate (I) with dimethyl sulfate in HMPT gives the corresponding ester (II), which by reaction with the sodium salt of dimethylsulfoxide (III) in DMSO affords the hemithioketal (IV). Finally, this compound is condensed with aminoguanidine (V) in DMSO/water.

参考文献 中间体
合成目标
【1】 Burgos, A.; Ellames, G.J.; Convenient synthesis of [2-C-14]-methylglyoxal bis(guanylhydrazone), [C-14]-mitoguazone. J Label Compd Radiopharm 1995, 36, 1, 93.
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) 44564 potassium acetate 127-08-2 C2H3KO2 详情 详情
(I) 44565 potassium acetate C2H3KO2 详情 详情
(II) 44566 methyl acetate 79-20-9 C3H6O2 详情 详情
(II) 44567 methyl acetate C3H6O2 详情 详情
(III) 44569 [(methoxysulfanyl)methyl]sodium C2H5NaOS 详情 详情
(IV) 10014 1-Hydroxy-1-(methylsulfanyl)acetone 74178-33-9 C4H8O2S 详情 详情
(IV) 44568 1-Hydroxy-1-(methylsulfanyl)acetone C4H8O2S 详情 详情
(V) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The oxidation of acetone (I) with butyl nitrite (II) with a catalytic amount of HCl gives methylglyoxal 1-oxime (III), which is then condensed with aminoguanidine (IV) in hot water acidified with HCl.

参考文献 中间体
合成目标
【1】 Nagaki, D.; Nishimura, T.; Hasegawa, K.; Toku, H.; Sakaguchi, H.; Yamazaki, C.; Antiviral compounds. IX. Synthesis and anti-influenza virus activity of bis-amidinohydrazones of glyoxal and methylglyoxal. Kitasato Arch Exp Med 1975, 48, 4, 171-181.
【2】 Serradell, M.N.; Eastland, G.W.; Castaner, J.; Mitoguazone. Drugs Fut 1984, 9, 3, 199.
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) 23199 2-Propanone; Acetone; beta-ketopropane; chevron acetone;propan-2-one； Dimethyl formaldehyde; Dimethyl ketone; dimethylketal; Ketone propane; Methyl ketone; Propanone; Pyroacetic acid; Pyroacetic ether 67-64-1 C3H6O 详情 详情
(II) 31340 butyl nitrite 544-16-1 C4H9NO2 详情 详情
(III) 30362 2-oxopropanal oxime 306-44-5 C3H5NO2 详情 详情
(IV) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情

合成路线3

该中间体在本合成路线中的序号：(II)

By condensation of 2,6-dichlorobenzaldehyde (I) and aminoguanidine carbonate (II).

参考文献 中间体
合成目标
【1】 Bundgaard, H.; Castaner, J.; Guanabenz. Drugs Fut 1976, 1, 11, 523.
【2】 Wuesthoff, F.; et al.; Novel hydrazine compounds and compositions containing them. BE 0661193; CH 453793; DE 1567104; FR 1455835; GB 1019120 .
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) 27507 2,6-dichlorobenzaldehyde 83-38-5 C7H4Cl2O 详情 详情
(II) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情

合成路线4

该中间体在本合成路线中的序号：(V)

The Grignard condensation of 2,3-dichloroiodobenzene (I) with CO2 by means of Mg / ether gives 2,3-dichlorobenzoic acid (II), which is converted to the corresponding acyl chloride (III) by refluxing with SOCl2.The reaction of (III) with cuprous cyanide and KI in refluxing xylene yields 2,3-dichlorobenzoyl cyanide (IV). Finally, this compound is cyclized with aminoguanidine (V) in DMSO.

参考文献 中间体
合成目标
【1】 Baxter, M.G.; Elphick, A.R.; Miller, A.A.; Sawyer, D.A. (Glaxo Wellcome plc); 1,2,4-Triazine derivs., process for preparing such cpds., pharmaceutical compsns. and intermediates utilized for this process. CA 1133938; EP 0021121 .
【2】 Castaner, J.; Prous, J.; Lamotrigine. Drugs Fut 1986, 11, 6, 456.
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) 24006 1,2-dichloro-3-iodobenzene 2401-21-0 C6H3Cl2I 详情 详情
(II) 24007 2,3-dichlorobenzoic acid 50-45-3 C7H4Cl2O2 详情 详情
(III) 24008 2,3-dichlorobenzoyl chloride 2905-60-4 C7H3Cl3O 详情 详情
(IV) 24009 2-(2,3-dichlorophenyl)-2-oxoacetonitrile; 2,3-Dichlorobenzoylcyanide 77668-42-9 C8H3Cl2NO 详情 详情
(V) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情

合成路线5

该中间体在本合成路线中的序号：(II)

Condensation of 2,3-dichlorobenzoyl cyanide (I) with aminoguanidine (II) by means of PPA in hot acetonitrile yields 2,3-dichlorobenzoyl cyanide amidinohydrazone (III), which is cyclized to the target 1,2,4-triazine by heating in refluxing propanol with or without DMSO.

参考文献 中间体
合成目标
【1】 Nadaka, V.; Lexner, J.; Kaspi, J. (Chemagis Ltd.); Process for preparing substd. benzoyl cyanide amidinohydrazones. EP 1127873 .
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) 24009 2-(2,3-dichlorophenyl)-2-oxoacetonitrile; 2,3-Dichlorobenzoylcyanide 77668-42-9 C8H3Cl2NO 详情 详情
(II) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情
(III) 52654 2-[cyano(phenyl)methylidene]-1-hydrazinecarboximidamide C9H9N5 详情 详情

合成路线6

该中间体在本合成路线中的序号：(VII)

Hydrogenation of 2,3-dichloronitrobenzene (I) with H2 over Ra-Ni in methanol gives 2,3-dichloroaniline (II), which is diazotized with NaNO2 and HCl and treated with CuCN to yield 2,3-dichlorobenzonitrile (III). Hydrolysis of the nitrile (III) with NaOH in refluxing methanol/water affords 2,3-dichlorobenzoic acid (IV), which is treated with hot SOCl2 to provide the corresponding acyl chloride (V). Reaction of (V) with CuCN and KI in refluxing chlorobenzene gives 2,3-dichlorobenzoyl cyanide (VI), which is condensed with aminoguanidine (VII) by means of H2SO4/TsOH in hot toluene to yield 2,3-dichlorobenzoyl cyanide amidinohydrazone (VIII). Finally, this compound is cyclized by treatment with NaOMe in refluxing methanol.

参考文献 中间体
合成目标
【1】 Srivastava, A.R.; Sasikumar, T.M.; Radhakrishnan, T.V. (RPG Life Sciences Ltd); A process for the preparation of 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine, commonly known as lamotrigine. WO 0149669 .
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) 52655 2,3-Dichloronitrobenzene; 1,2-Dichloro-3-Nitrobenzene; Nitro-o-dichlorobenzene 3209-22-1 C6H3Cl2NO2 详情 详情
(II) 28562 2,3-dichlorophenylamine 608-27-5 C6H5Cl2N 详情 详情
(III) 30204 2,3-dichlorobenzonitrile 6574-97-6 C7H3Cl2N 详情 详情
(IV) 24007 2,3-dichlorobenzoic acid 50-45-3 C7H4Cl2O2 详情 详情
(V) 24008 2,3-dichlorobenzoyl chloride 2905-60-4 C7H3Cl3O 详情 详情
(VI) 24009 2-(2,3-dichlorophenyl)-2-oxoacetonitrile; 2,3-Dichlorobenzoylcyanide 77668-42-9 C8H3Cl2NO 详情 详情
(VII) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情
(VIII) 52654 2-[cyano(phenyl)methylidene]-1-hydrazinecarboximidamide C9H9N5 详情 详情

合成路线7

该中间体在本合成路线中的序号：(I)

Condensation of aminoguanidine carbonate (I) with formic acid gives 3-aminotriazole (II), which by treatment with concentrated nitric acid in a sodium nitrite solution gives 3-nitrotriazole (III). N-Alkylation of (III) with bromoacetic acid ethyl ester affords 2-(3-nitro-1,2,4-triazol-1-yl)acetic acid ethyl ester (IV). Reaction of (IV) with 2-methoxyethylamine in dioxane yields AK-2123.

参考文献 中间体
合成目标
【1】 Horning, E.C.; Organic Syntheses, Vol. 3, 1st Ed. University of Missouri 1995, 95.
【2】 Sugita, T.; Masuoka, M.; Nishikawa, Y.; Nishimoto, S.; Zhuo, L.; Sasai, K.; Kagiya, T.; Nitrotriazoles bearing sulfur-substituted side chains: Preparation and characterization as hypoxic cell radiosensitizers. Anti-Cancer Drug Des 1992, 7, 277-84.
【3】 Huan, L.C.; Rong, S.; AK-2123. Drugs Fut 1995, 20, 7, 659.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
16640 Ethyl 2-bromoacetate; Ethyl bromoacetate 105-36-2 C4H7BrO2 详情 详情
34675 2-methoxyethylamine; 2-methoxy-1-ethanamine 109-85-3 C3H9NO 详情 详情
(I) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情
(II) 12475 1H-1,2,4-Triazol-3-amine; 1H-1,2,4-Triazol-3-ylamine 61-82-5 C2H4N4 详情 详情
(III) 12476 3-Nitro-1H-1,2,4-triazole; 3-Nitro-1,2,4-triazole 24807-55-4 C2H2N4O2 详情 详情
(IV) 12477 ethyl 2-(3-nitro-1H-1,2,4-triazol-1-yl)acetate C6H8N4O4 详情 详情

合成路线8

该中间体在本合成路线中的序号：(VII)

Reaction of 4-acetylpyridine (I) with hot dimethylformamide dimethyl acetal (II) gives the enamino ketone (III), which is then condensed with (3-amino-1H-pyrazol-4-yl)(2-pyridyl)methanone (IV) in boiling acetic acid. Intermediate (IV), (3-amino-1H-pyrazol-4-yl)(2-pyrid-yl)methanone, is obtained by condensation of 3-oxo-3-(2-pyridyl)propionitrile (V) with dimethylformamide dimethyl acetal (II) to provide 2-(dimethylaminomethylene)-3-oxo-3-(2-pyridyl)propionitrile (VI), which is finally coupled with aminoguanidine nitrate (VII) by means of 10N NaOH in refluxing EtOH

参考文献 中间体
合成目标
【1】 Castaner, J.; Silvestre, J.S.; Chilman-Blair, K.; Ocinaplon. Drugs Fut 2003, 28, 2, 115-120.
【2】 Tomcufcik, A.S.; Dusza, J.P. (Wyeth); (3-Amino-1H-pyrazol-4-yl)(aryl)methanones. EP 0129846; JP 1985013764; US 4900836 .
【3】 Dusza, J.P.; Tomcufcik, A.S.; Albright, J.D. (Wyeth); Aryl and heteroaryl 7-(aryl and heteroaryl)-pyrazolo[1,5-a]pyrimidin-3-ylmethanones. DE 3422844; EP 0129847; JP 1985019788 .
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) 59510 4-Acetylpyridine; Methyl 4-pyridyl ketone 1122-54-9 C7H7NO 详情 详情
(II) 11984 N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal 4637-24-5 C5H13NO2 详情 详情
(III) 59511 (E)-3-(dimethylamino)-1-(4-pyridinyl)-2-propen-1-one C10H12N2O 详情 详情
(IV) 59512 (3-amino-1H-pyrazol-4-yl)(2-pyridinyl)methanone C9H8N4O 详情 详情
(V) 59513 3-oxo-3-(2-pyridinyl)propanenitrile C8H6N2O 详情 详情
(VI) 59514 (E)-3-(dimethylamino)-2-(2-pyridinylcarbonyl)-2-propenenitrile C11H11N3O 详情 详情
(VII) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情

合成路线9

该中间体在本合成路线中的序号：(IV)

The reaction of decanedioyl dichloride (I) with 3,5-diacetylaniline (II) by means of pyridine in dichloromethane gives the corresponding diamide (III), which is condensed with aminoguanidine (IV) in refluxing aqueous ethanol to afford the target tetrakis amidinohydrazone.

参考文献 中间体
合成目标
【1】 Cerami, A.; Ulrich, P.; Tracey, K.J.; Bianchi, M. (Picower Institute for Medical Research); Guanylhydrazones for treating inflammatory conditions. EP 0746312; EP 1160240; US 5599984; WO 9519767 .
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) 53486 Sebacic acid chloride; Sebacoyl chloride; Sebacoyl dichloride; Sebacic acid dichloride 111-19-3 C10H16Cl2O2 详情 详情
(II) 53487 1-(3-acetyl-5-aminophenyl)-1-ethanone n/a C10H11NO2 详情 详情
(III) 53488 N1,N10-bis(3,5-diacetylphenyl)decanediamide n/a C30H36N2O6 详情 详情
(IV) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情

合成路线10

该中间体在本合成路线中的序号：(VIII)

Orcinol (I) is first derivatized to (III) by reaction with sulfonyl chloride (II) in a mixture of aqueous NaHCO3 (sat) and Et2O. Monosulfonate (III) undergoes Mitsunobu reaction with monobenzylated diol (IV) in the presence of PPh3 and DEAD in dichloromethane to yield derivative (V), which is then debenzylated by hydrogenolysis over Pd/C in MeOH, or in THF/HCl/dioxane, to afford (VI). Alcohol (VI) is oxidized with SO3·pyr complex in DMSO/dichloromethane in the presence of DIEA to provide aldehyde (VIII), which finally reacts with aminoguanidine nitrate in EtOH in the presence of HCl/dioxane.

参考文献 中间体
合成目标
【1】 Soll, R.M.; Lu, T.; Tomczuk, B.; et al.; Amidinohydrazones as guanidine bioisosteres: Application to a new class of potent, selective and orally bioavailable, non-amide-based small-molecule thrombin inhibitors. Bioorg Med Chem Lett 2000, 10, 1, 1.
【2】 Soll, R.M.; Lu, T.; Fedde, C.L.; Tomczuk, B.E.; Illig, C. (3-Dimensional Pharmaceuticals, Inc.); Amidinohydrazones as protease inhibitors. EP 0906091; JP 2000507588; US 5891909; WO 9736580 .
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) 27257 5-Methyl-1,3-benzenediol; Orcinol 505-15-4 C7H8O2 详情 详情
(II) 30817 2-chlorobenzenesulfonyl chloride 2905-23-9 C6H4Cl2O2S 详情 详情
(III) 30818 3-hydroxy-5-methylphenyl 2-chlorobenzenesulfonate C13H11ClO4S 详情 详情
(IV) 14687 3-(benzyloxy)-1-propanol; 3-(Benzyloxy)propanol 4799-68-2 C10H14O2 详情 详情
(V) 30819 3-[3-(benzyloxy)propoxy]-5-methylphenyl 2-chlorobenzenesulfonate C23H23ClO5S 详情 详情
(VI) 30820 3-(3-hydroxypropoxy)-5-methylphenyl 2-chlorobenzenesulfonate C16H17ClO5S 详情 详情
(VII) 30821 3-methyl-5-(3-oxopropoxy)phenyl 2-chlorobenzenesulfonate C16H15ClO5S 详情 详情
(VIII) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情

合成路线11

该中间体在本合成路线中的序号：(V)

Condensation of 2-acetylthiophene (I) with dimethylformamide dimethylacetal produced enaminone (II), which was subsequently cyclized to the isoxazole (III) upon treatment with hydroxylamine. Further condensation of (III) with dimethylformamide dimethylacetal, with concomitant isoxazole ring opening, gave rise to the enamino nitrile (IV). This was then cyclized with aminoguanidine nitrate (V) under basic conditions to furnish the intermediate aminopyrazole (VI).

参考文献 中间体
合成目标
【2】 Tomcufcik, A.S.; Dusza, J.P.; Albright, J.D.; Beer, B. (Wyeth); N-Methyl-N-(-[3-[-2-thienylcarbonyl]-pyrazol-[1,5-alpha]-pyrimidin-7-yl]phenyl)acetamide and compsns. and methods related thereto. US 6399621 .
【1】 Sorbera, L.A.; Castaner, J.; Martin, L.; Indiplon. Drugs Fut 2003, 28, 8, 739.
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) 24490 1-(2-Thienyl)-1-ethanone; 2-Acetylthiophene 88-15-3 C6H6OS 详情 详情
(II) 59943 (E)-3-(dimethylamino)-1-(2-thienyl)-2-propen-1-one C9H11NOS 详情 详情
(III) 59944 5-(2-thienyl)isoxazole C7H5NOS 详情 详情
(IV) 59945 (E)-3-(dimethylamino)-2-(2-thienylcarbonyl)-2-propenenitrile C10H10N2OS 详情 详情
(V) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情
(VI) 59946 (3-amino-1H-pyrazol-4-yl)(2-thienyl)methanone C8H7N3OS 详情 详情

合成路线12

该中间体在本合成路线中的序号：(V)

Reaction of 3-(acetamido)acetophenone (VIII) with iodomethane and NaH gives 3-(N-methylacetamido)acetophenone (XXVIII), which is mixed with 3-oxo-3-(2-thienyl)propionitrile (VII) and treated with dimethylformamide dimethylacetal to yield a mixture of the dimethylaminomethylene derivatives (IV) and (X). This mixture, without isolation, is cyclized with aminoguanidine (V) by treatment first with NaOH in ethanol and then with refluxing AcOH.

参考文献 中间体
合成目标
【1】 Sorbera, L.A.; Castaner, J.; Martin, L.; Indiplon. Drugs Fut 2003, 28, 8, 739.
【2】 Wilcoxen, K.M.; Gross, R.S. (Neurocrine Biosciences Inc.); Synthesis of substd. pyrazolopyrimidines. WO 0110868 .
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) 59945 (E)-3-(dimethylamino)-2-(2-thienylcarbonyl)-2-propenenitrile C10H10N2OS 详情 详情
(V) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情
(VII) 62972 3-oxo-3-(2-thienyl)propanenitrile C7H5NOS 详情 详情
(VIII) 11983 3'-Acetamidoacetophane; m-Acetamidoacetophenone; N-(3-Acetylphenyl)acetamide 7463-31-2 C10H11NO2 详情 详情
(X) 59947 N-{3-[(E)-3-(dimethylamino)-2-propenoyl]phenyl}-N-methylacetamide C14H18N2O2 详情 详情
(XXVIII) 62971 N-(3-acetylphenyl)-N-methylacetamide C11H13NO2 详情 详情

合成路线13

该中间体在本合成路线中的序号：(VIII)

2-Chlorobenzenesulfonyl chloride (I) was coupled to orcinol (II) to give sulfonate (III). Subsequent condensation of (III) with 3-benzyloxypropanol (IV) under Mitsunobu conditions afforded ether (V). After hydrogenolytic deprotection of the benzyl group, Swern oxidation of the resulting alcohol (VI) with DMSO and SO3-pyridine complex provided aldehyde (VII). The title amidinohydrazone was then obtained by treatment of (VII) with aminoguanidine nitrate (VIII).

参考文献 中间体
合成目标
【1】 Soll, R.M.; Lu, T.; Fedde, C.L.; Tomczuk, B.E.; Illig, C. (3-Dimensional Pharmaceuticals, Inc.); Amidinohydrazones as protease inhibitors. EP 0906091; JP 2000507588; US 5891909; WO 9736580 .
【2】 Tomczuk, B.E.; Stagnaro, T.P.; Fedde, C.L.; Lu, T.; Markotan, T.P.; Illig, C.R.; Soll, R.M. (3-Dimensional Pharmaceuticals, Inc.); Aminoguanidines and alkoxyguanidines as protease inhibitors. EP 0944590; WO 9823565 .
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) 30817 2-chlorobenzenesulfonyl chloride 2905-23-9 C6H4Cl2O2S 详情 详情
(II) 27257 5-Methyl-1,3-benzenediol; Orcinol 505-15-4 C7H8O2 详情 详情
(III) 30818 3-hydroxy-5-methylphenyl 2-chlorobenzenesulfonate C13H11ClO4S 详情 详情
(IV) 14687 3-(benzyloxy)-1-propanol; 3-(Benzyloxy)propanol 4799-68-2 C10H14O2 详情 详情
(V) 30819 3-[3-(benzyloxy)propoxy]-5-methylphenyl 2-chlorobenzenesulfonate C23H23ClO5S 详情 详情
(VI) 30820 3-(3-hydroxypropoxy)-5-methylphenyl 2-chlorobenzenesulfonate C16H17ClO5S 详情 详情
(VII) 30821 3-methyl-5-(3-oxopropoxy)phenyl 2-chlorobenzenesulfonate C16H15ClO5S 详情 详情
(VIII) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情

合成路线14

该中间体在本合成路线中的序号：(II)

The condensation of nitroenamine (I) with aminoguanidine (II) afforded compound (III), which was subsequently cyclized to the title pyrazole by treatment with NaOH.

参考文献 中间体
合成目标
【1】 Makarov, V.; et al.; 4-Nitropyrazole derivatives as new exogenic donors of nitric oxide. 16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000, Abst PA-120.
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) 46029 (E)-3-amino-3-(dimethylamino)-2-nitro-2-propenenitrile C5H8N4O2 详情 详情
(II) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情
(III) 46030 2-[(E)-1-amino-2-cyano-2-nitroethenyl]-1-hydrazinecarboximidamide C4H7N7O2 详情 详情

合成路线15

该中间体在本合成路线中的序号：(V)

Amination of cyclohexanedione derivative (I) with ammonium acetate in refluxing ethanol affords compound (II), which is converted into tetrahydroquinolinone derivative (IV) by condensation with 3-oxobutylaldehyde dimethylacetal (III) and cyclization by means of KOH in refluxing EtOH. The desired compound is finally obtained by first reaction of ketone (IV) with aminoguanidine hydrochloride (V) in refluxing EtOH/HCl, followed by formation of the corresponding dimethanesulfonate salt by treatment with methanesulfonic acid.

参考文献 中间体
合成目标
【1】 Fukumoto, S.; et al.; Novel, non-acylguanidine-type Na+/H+ exchanger inhibitors: Synthesis and pharmacology of 5-tetrahydroquinolinylidene aminoguanidine derivatives. J Med Chem 2002, 45, 14, 3009.
【3】 Shiraishi, M.; Fukumoto, S.; Kusumoto, K. (Takeda Chemical Industries, Ltd.); Aminoguanidine hydrazone derivs., process for producing the same and drugs thereof. EP 1057812; JP 2000191641; WO 9942442 .
【2】 Imamiya, E.; Fujiwara, S.; Watanabe, T.; Shiraishi, M.; Fukumoto, S.; Kusumoto, K.; Novel, non-acylguanidine type Na+/H+ exchanger inhibitors: Synthesis and biological evaluation of tetrahydroquinolinylidene aminoguanidine derivatives. 20th Symp Med Chem (Dec 6 2000, Tokyo) 2000, Abst 2P-02.
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) 48879 5-(5-fluoro-2-methylphenyl)-1,3-cyclohexanedione C13H13FO2 详情 详情
(II) 48880 3-amino-5-(5-fluoro-2-methylphenyl)-2-cyclohexen-1-one C13H14FNO 详情 详情
(III) 48881 Acetoacetaldehyde Dimethylacetal; 1,1-dimethoxy-3-butanone; 3-Ketobutyraldehyde dimethyl acetal; 3-Ketobutyric aAldehyde 1-dimethylacetal; 3-Oxobutyraldehyde dimethylacetal; 4,4-Dimethoxy-2-butanone 5436-21-5 C6H12O3 详情 详情
(IV) 48882 7-(5-fluoro-2-methylphenyl)-4-methyl-7,8-dihydro-5(6H)-quinolinone C17H16FNO 详情 详情
(V) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情

合成路线16

该中间体在本合成路线中的序号：(II)

The title compound is prepared by condensation of 2-chloro-3,4-dimethoxybenzaldehyde (I) with aminoguanidine bicarbonate (II) in the presence of HOAc in refluxing MeOH.

参考文献 中间体
合成目标
【1】 Skottner, A.; Lundstedt, T.; Seifert, E.; Veveris, M.; Piskunova, I.; Rozhkov, E.; Wikberg, J.; Pett, C.P.; Kalvins, I.; Andrianov, V.; Semenikhina, V.; Dambrova, M. (Melacure Therapeutics); Guanidine derivs. and their use in the production of a medicament for blocking xanthine oxidase/dehydrogenase. WO 0125192 .
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) 57570 2-chloro-3,4-dimethoxybenzaldehyde C9H9ClO3 详情 详情
(II) 10015 1-Hydrazinecarboximidamide; Hydrazinecarboximidamide 79-17-4 CH6N4 详情 详情
Extended Information