N-Methyl-N-[(E)-1-(methylsulfanyl)-2-nitroethenyl]amine; (E)-N-Methyl-1-(methylsulfanyl)-2-nitro-1-ethenamine; (E)-1-Methylthio-1-methylamino-2-nitroethylene -Drug Synthesis Database

【结构式】

【分子编号】13852

【品名】N-Methyl-N-[(E)-1-(methylsulfanyl)-2-nitroethenyl]amine; (E)-N-Methyl-1-(methylsulfanyl)-2-nitro-1-ethenamine; (E)-1-Methylthio-1-methylamino-2-nitroethylene

【CA登记号】61832-41-5

【分子式】C₄H₈N₂O₂S

【分子量】148.1858

【元素组成】C 32.42% H 5.44% N 18.9% O 21.59% S 21.64%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(VII)

The cyclization of dimethylaminothioacetamide (I) with ethyl bromopyruvate (II) in refluxing ethanol gives ethyl 2-(dimethylaminomethyl)-4-thiazolecarboxylate (III), which is reduced with lithium triethyl borohydride in THF yielding 2-(dimethylaminomethyl)-4-thiazolemethanol (IV). The condensation of (IV) with 2-aminoethanethiol (V) by means of 48% HBr affords 2-(dimethylaminomethyl)-4-(2-aminoethylthiomethyl)thiazole (VI), which is finally condensed with 1-(methylthio)-2-nitro-N-methylethyleneamine (VII) in water.

参考文献中间体

合成目标

【1】 Pioch, R.P. (Eli Lilly and Company); N-Methyl-N'-2-[[(2-dimethylaminomethyl)-4-thiazolyl]methylthio]ethyl-2-nitro-1,1-ethenediamine. EP 0049618; GB 2084581; JP 57091980; US 4375547 .
【2】 Serradell, M.N.; Castaner, J.; Nizatidine. Drugs Fut 1984, 9, 9, 655.

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)	30602	2-(dimethylamino)ethanethioamide		C₄H₁₀N₂S	详情	详情
(II)	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
(III)	30603	ethyl 2-[(dimethylamino)methyl]-1,3-thiazole-4-carboxylate		C₉H₁₄N₂O₂S	详情	详情
(IV)	30604	[2-[(dimethylamino)methyl]-1,3-thiazol-4-yl]methanol		C₇H₁₂N₂OS	详情	详情
(V)	13186	2-Aminoethanethiol; 2-Amino-1-ethanethiol; 2-Aminoethylhydrosulfide; Cysteamine	60-23-1	C₂H₇NS	详情	详情
(VI)	30605	N-[(4-[[(2-aminoethyl)sulfanyl]methyl]-1,3-thiazol-2-yl)methyl]-N,N-dimethylamine; 2-[([2-[(dimethylamino)methyl]-1,3-thiazol-4-yl]methyl)sulfanyl]-1-ethanamine		C₉H₁₇N₃S₂	详情	详情
(VII)	13852	N-Methyl-N-[(E)-1-(methylsulfanyl)-2-nitroethenyl]amine; (E)-N-Methyl-1-(methylsulfanyl)-2-nitro-1-ethenamine; (E)-1-Methylthio-1-methylamino-2-nitroethylene	61832-41-5	C₄H₈N₂O₂S	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 reaction of 5-dimethylaminomethyl-2-furanylmethanol (I) with 2-mercaptoethylamine (II) by means of aqueous HCl gives 2-[[(5-dimethylamino-methyl-2-furanyl)methylthio]ethaneamine (III), which is then condensed with N-methyl-1-methylthio-2-nitrotheneamine (IV) by heating at 120 C. Compound (IV) is obtained by reaction of 1,1-bis(methylthio)-2-nitroethene (V) with methylamine in refluxing ethanol.

参考文献中间体

合成目标

【1】 Price, B.J.; Bradshaw, J.; Clitherow, J.W. (Allen & Hansburys Ltd.); Aminoalkyl furan derivatives.. DE 2734070; FR 2360587; US 4128658 .
【2】 Serradell, M.N.; Blancafort, P.; Castaner, J.; Hillier, K.; Ranitidine. Drugs Fut 1979, 4, 9, 663.

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)	13849	[5-[(dimethylamino)methyl]-2-furyl]methanol		C₈H₁₃NO₂	详情	详情
(II)	13186	2-Aminoethanethiol; 2-Amino-1-ethanethiol; 2-Aminoethylhydrosulfide; Cysteamine	60-23-1	C₂H₇NS	详情	详情
(III)	13851	2-[([5-[(Dimethylamino)methyl]-2-furyl]methyl)sulfanyl]-1-ethanamine; N-[(5-[[(2-Aminoethyl)sulfanyl]methyl]-2-furyl)methyl]-N,N-dimethylamine		C₁₀H₁₈N₂OS	详情	详情
(IV)	13852	N-Methyl-N-[(E)-1-(methylsulfanyl)-2-nitroethenyl]amine; (E)-N-Methyl-1-(methylsulfanyl)-2-nitro-1-ethenamine; (E)-1-Methylthio-1-methylamino-2-nitroethylene	61832-41-5	C₄H₈N₂O₂S	详情	详情
(V)	13853	Methyl 1-(methylsulfanyl)-2-nitrovinyl sulfide; 1,1-Bis(methylthio)-2-nitroethylene; 1,1-Bis(methylsulfanyl)-2-nitroethylene	13623-94-4	C₄H₇NO₂S₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

The reaction of 2-furan-methanol (I) with dimethylamine and formaldehyde gives 5-(dimethylaminomethyl)furan-2-methanol (II), which is condensed with 2-sulfanylethylamine (III) yielding 2-[5-(dimethylaminomethyl)furan-2-ylsulfanyl]ethylamine (IV). The condensation of (IV) with 1-(methylamino)-1-(methylsulfanyl)-2-nitroethylene (V), obtained from 1,1,-bis(methylsulfanyl)-2-nitroethylene (VI) and methylamine, in hot acetone, or by heating at 100-120 C affords N-[2-[5-(dimethylaminomethyl)furan-2-ylmethylsulfanyl]ethyl]- N'-methyl-2-nitroethylene-1,1-diamine (VII) , which is finally complexed with bismuth (+3) citrate (VIII), obtained by reaction of NO3BiO with citric acid (IX) in hot water.

参考文献中间体

合成目标

【1】 Castaner, J.; Rabasseda, X.; Mealy, N.; Ranitidine Bismuth Citrate. Drugs Fut 1995, 20, 5, 480.
【2】 Clitherow, J.W. (Glaxo Wellcome plc); Ranitidine derivs. BE 1003254; CH 679582; GB 2220937; JP 1990117684; US 5008256 .
【3】 Bradshaw, J.; Price, B.J.; Clitherow, J.W.; Aminoalkyl furan derivs. GB 1565966 .

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)	13848	2-Furylmethanol; Furfuryl Alcohol	98-00-0	C₅H₆O₂	详情	详情
(II)	13849	[5-[(dimethylamino)methyl]-2-furyl]methanol		C₈H₁₃NO₂	详情	详情
(III)	13186	2-Aminoethanethiol; 2-Amino-1-ethanethiol; 2-Aminoethylhydrosulfide; Cysteamine	60-23-1	C₂H₇NS	详情	详情
(IV)	13851	2-[([5-[(Dimethylamino)methyl]-2-furyl]methyl)sulfanyl]-1-ethanamine; N-[(5-[[(2-Aminoethyl)sulfanyl]methyl]-2-furyl)methyl]-N,N-dimethylamine		C₁₀H₁₈N₂OS	详情	详情
(V)	13852	N-Methyl-N-[(E)-1-(methylsulfanyl)-2-nitroethenyl]amine; (E)-N-Methyl-1-(methylsulfanyl)-2-nitro-1-ethenamine; (E)-1-Methylthio-1-methylamino-2-nitroethylene	61832-41-5	C₄H₈N₂O₂S	详情	详情
(VI)	13853	Methyl 1-(methylsulfanyl)-2-nitrovinyl sulfide; 1,1-Bis(methylthio)-2-nitroethylene; 1,1-Bis(methylsulfanyl)-2-nitroethylene	13623-94-4	C₄H₇NO₂S₂	详情	详情
(VII)	13854	N-[2-[([5-[(Dimethylamino)methyl]-2-furyl]methyl)sulfanyl]ethyl]-N-[(E)-1-(methylamino)-2-nitroethenyl]amine; (E)-N(1)-[2-[([5-[(Dimethylamino)methyl]-2-furyl]methyl)sulfanyl]ethyl]-N(1)-methyl-2-nitro-1,1-ethenediamine; Ranitidine	66357-35-5	C₁₃H₂₂N₄O₃S	详情	详情
(VIII)	13855	bismuth(3+) 2-hydroxy-1,2,3-propanetricarboxylate; Bismuth Citrate	813-93-4	C₆H₅BiO₇	详情	详情
(IX)	13856	2-Hydroxy-1,2,3-propanetricarboxylic acid; Citric acid	77-92-9	C₆H₈O₇	详情	详情

Extended Information