Methyl 1-(methylsulfanyl)-2-nitrovinyl sulfide; 1,1-Bis(methylthio)-2-nitroethylene; 1,1-Bis(methylsulfanyl)-2-nitroethylene -Drug Synthesis Database

【结构式】

【分子编号】13853

【品名】Methyl 1-(methylsulfanyl)-2-nitrovinyl sulfide; 1,1-Bis(methylthio)-2-nitroethylene; 1,1-Bis(methylsulfanyl)-2-nitroethylene

【CA登记号】13623-94-4

【分子式】C₄H₇NO₂S₂

【分子量】165.23712

【元素组成】C 29.08% H 4.27% N 8.48% O 19.37% S 38.81%

与该中间体有关的原料药合成路线共 6 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1

该中间体在本合成路线中的序号：(V)

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2

该中间体在本合成路线中的序号：(VII)

The Mannich reaction of tricyclo[2.2. 1.0(2,6)]hept-3-ylamine hydrochloride (I) with 2-furanylmethanol (II) and paraformaldehyde (III) in ethanol gives 5-(tricyclo[2.2. 1.0(2,6)]hept-3-ylamino)methyl-2-furanyl methanol (IV). The reaction of compound (IV) with 2 mercaptoethylamine (V) by means of concentrated HCl affords 2 [[[5-[(tricyclo[2.2.1.0(2,6)]hept-3-yl-amino(methyl]-2-furanyl]methyl]thio]etheneamine (VI), which is converted with 1 1-bis(methylthio)-2-nitroethene (VII) in isopropyl alcohol by heating at 70 C to N-[2-[[[5 [(tricyclo[2.2.1.O(2,6)]hept-3-ylamino)methyl]-2-furanyl]methyl]thio]ethyl]-1-(methylthio)-2-nitroetheneamine (VIII). Compound (VIII) is then treated with excess methylamine in ethanol at 0 C, followed by treatment with ethereal HCl to give the desired-N-[2-[[[5 [(tricyclo[2.2. 1.0(2,6)]hept-3-ylamino)methyl]-2 furanyl]methyl]thio]ethyl] N'- methyl-2-nitro-1,1-ethenediaminehydrochloride.

参考文献中间体

合成目标

【1】 Emig, P.; et al. (Degussa-Huls AG); Novel ethenediamine and guanidine derivatives. DE 3343884 .
【2】 Castaner, J.; Prous, J.; D-16637. Drugs Fut 1986, 11, 1, 14.

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)	24124	tricyclo[2.2.1.0(2,6)]hept-3-ylamine		C₇H₁₁N	详情	详情
(II)	13848	2-Furylmethanol; Furfuryl Alcohol	98-00-0	C₅H₆O₂	详情	详情
(IV)	24126	[5-[(tricyclo[2.2.1.0(2,6)]hept-3-ylamino)methyl]-2-furyl]methanol		C₁₃H₁₇NO₂	详情	详情
(V)	13186	2-Aminoethanethiol; 2-Amino-1-ethanethiol; 2-Aminoethylhydrosulfide; Cysteamine	60-23-1	C₂H₇NS	详情	详情
(VI)	24128	N-[(5-[[(2-aminoethyl)sulfanyl]methyl]-2-furyl)methyl]-N-tricyclo[2.2.1.0(2,6)]hept-3-ylamine		C₁₅H₂₂N₂OS	详情	详情
(VII)	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
(VIII)	24130	N-[(Z)-1-(methylsulfanyl)-2-nitroethenyl]-N-[2-[([5-[(tricyclo[2.2.1.0(2,6)]hept-3-ylamino)methyl]-2-furyl]methyl)sulfanyl]ethyl]amine		C₁₈H₂₅N₃O₃S₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

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

合成路线4

该中间体在本合成路线中的序号：(II)

Condensation of primary amine (I) with 1,1-bis(methylthio)-2-nitroethene (II) in refluxing acetonitrile afforded adduct (III). Displacement of the methylthio group of (III) by hydrazine yielded compound (IV), which was finally condensed with glyoxal (V) in the presence of Triton B to produce the target pyridazine.

参考文献中间体

合成目标

【1】 Chapman, J.M. Jr.; Sowell, W.; Tang, Y.; Kosh, J.W.; Valli, M.J.; Synthesis and cholinergic properties of N-aryl-2-[[[5-[(dimethylamino)methyl]-2-furanyl]methyl]thio]ethylamino analogs of ranitidine. J Med Chem 1992, 35, 17, 3141.

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)	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
(II)	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
(III)	32555	(E)-N-[2-[([5-[(dimethylamino)methyl]-2-furyl]methyl)sulfanyl]ethyl]-1-(methylsulfanyl)-2-nitro-1-ethenamine; N-[2-[([5-[(dimethylamino)methyl]-2-furyl]methyl)sulfanyl]ethyl]-N-[(E)-1-(methylsulfanyl)-2-nitroethenyl]amine		C₁₃H₂₁N₃O₃S₂	详情	详情
(IV)	32556	N-[2-[([5-[(dimethylamino)methyl]-2-furyl]methyl)sulfanyl]ethyl]-N-[(E)-1-hydrazino-2-nitroethenyl]amine; (E)-N-[2-[([5-[(dimethylamino)methyl]-2-furyl]methyl)sulfanyl]ethyl]-1-hydrazino-2-nitro-1-ethenamine		C₁₂H₂₁N₅O₃S	详情	详情
(V)	32557	glyoxal; 2-oxoacetaldehyde	107-22-2	C₂H₂O₂	详情	详情

合成路线5

该中间体在本合成路线中的序号：(VI)

Condensation of chloropyridine (I) with cyclooctylamine (II) provided the cyclooctylaminopyridine (III). The aminonitroethylene derivative (VI) was prepared by reaction of 1,1-bis(methylsulfanyl)-2-nitroethylene (IV) with cyclohexylamine (V) in refluxing EtOH. Subsequent condensation of this intermediate with the sodium salt of sulfonamide (III) yielded the title compound.

参考文献中间体

合成目标

【1】 Masereel, B.; Wouters, J.; Pochet, L.; Lambert, D.; Design, synthesis, and anticonvulsant activity of 1-(pyrid-3-ylsulfonamido)-2-nitroethylenes. J Med Chem 1998, 41, 17, 3239.

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)	22151	4-chloro-3-pyridinesulfonamide		C₅H₅ClN₂O₂S	详情	详情
(II)	17996	3-(1H-pyrazol-5-yl)benzaldehyde		C₁₀H₈N₂O	详情	详情
(II)	22152	cyclooctanamine; cyclooctylamine	5452-37-9	C₈H₁₇N	详情	详情
(III)	22153	4-(cyclooctylamino)-3-pyridinesulfonamide		C₁₃H₂₁N₃O₂S	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
(VI)	22156	N-[(E)-1-(methylsulfanyl)-2-nitroethenyl]cyclohexanamine; N-cyclohexyl-N-[(E)-1-(methylsulfanyl)-2-nitroethenyl]amine		C₉H₁₆N₂O₂S	详情	详情

合成路线6

该中间体在本合成路线中的序号：(X)

Reaction of 6-chloronicotinic acid (I) with methyllithium lithium bromide complex gives methyl ketone (II), which is treated with dibromobarbituric acid (III) in refluxing THF to afford bromoketone (IV). Asymmetric reduction of (IV) with (-)-DIP-chloride [(-)-B-chlorodiisopinocampheylborane] provides bromohydrin (V), which is converted into epoxide (VI) by treatment with NaOH in THF/H2O. Opening of the epoxide moiety of (VI) with p-nitrophenethylamine hydrochloride (VII) in MeOH in the presence of Et3N followed by N-protection with Boc2O in THF yields ethanolamine (VIII), which is then hydrogenated over Ni-Raney in EtOH/NaOH to furnish dechlorinated aniline (IX). Condensation of (IX) with 1,1-bis(methylsulfanyl)-2-nitroethylene (X) in isopropanol gives compound (XI), which is then subjected to reaction with aniline (XII) in isopropanol to afford nitroethylenediamine (XIII). Finally, the desired product is obtained by Boc removal of (XIII) by treatment with TFA in CH2Cl2.

参考文献中间体

合成目标

【1】 Wyvratt, M.J.; Cascieri, M.A.; Liu, Y.; Parmee, E.R.; Tota, L.; Brockunier, L.L.; Candelore, M.R.; Fisher, M.H.; Weber, A.E.; Human beta3 adrenergic receptor agonists containing cyanoguanidine and nitroethylenediamide moieties. Bioorg Med Chem Lett 2001, 11, 3, 379.
【2】 Naylor, E.M.; Colandrea, V.J.; Candelore, M.R.; Cascieri, M.A.; Colwell, L.F. Jr; Deng, L.; Feeney, W.P.; Forrest, M.J.; Hom, G.J.; MacIntyre, D.E.; Strader, C.D.; Tota, L.; Wang, P.R.; Wyvratt, M.J.; Fisher, M.H.; Weber, A.E.; 3-Pyridylethanolamines: Potent and selective human beta3 adrenergic receptor agonists. Bioorg Med Chem Lett 1998, 8, 21, 3087.

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)	12996	6-Chloronicotinic acid	5326-23-8	C₆H₄ClNO₂	详情	详情
(II)	26555	1-(6-chloro-3-pyridinyl)-1-ethanone		C₇H₆ClNO	详情	详情
(III)	26556	5,5-dibromo-2,4,6(1H,3H,5H)-pyrimidinetrione	511-67-1	C₄H₂Br₂N₂O₃	详情	详情
(IV)	26557	2-bromo-1-(6-chloro-3-pyridinyl)-1-ethanone		C₇H₅BrClNO	详情	详情
(V)	26558	(1R)-2-bromo-1-(6-chloro-3-pyridinyl)-1-ethanol		C₇H₇BrClNO	详情	详情
(VI)	26559	2-chloro-5-[(2R)oxiranyl]pyridine		C₇H₆ClNO	详情	详情
(VII)	26560	4-nitrophenethylamine	24954-67-4	C₈H₁₀N₂O₂	详情	详情
(VIII)	26562	tert-butyl (2R)-2-(6-chloro-3-pyridinyl)-2-hydroxyethyl(4-nitrophenethyl)carbamate		C₂₀H₂₄ClN₃O₅	详情	详情
(IX)	26553	tert-butyl 4-aminophenethyl[(2R)-2-hydroxy-2-(3-pyridinyl)ethyl]carbamate		C₂₀H₂₇N₃O₃	详情	详情
(X)	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
(XI)	48294	tert-butyl (2R)-2-hydroxy-2-(3-pyridinyl)ethyl(4-[[(Z)-1-(methylsulfanyl)-2-nitroethenyl]amino]phenethyl)carbamate		C₂₃H₃₀N₄O₅S	详情	详情
(XII)	48295	3-aminobenzamide	3544-24-9	C₇H₈N₂O	详情	详情
(XIII)	48296	tert-butyl 4-([(Z)-1-[3-(aminocarbonyl)anilino]-2-nitroethenyl]amino)phenethyl[(2R)-2-hydroxy-2-(3-pyridinyl)ethyl]carbamate		C₂₉H₃₄N₆O₆	详情	详情

Extended Information