bismuth(3+) 2-hydroxy-1,2,3-propanetricarboxylate; Bismuth Citrate -Drug Synthesis Database

【结构式】

【分子编号】13855

【品名】bismuth(3+) 2-hydroxy-1,2,3-propanetricarboxylate; Bismuth Citrate

【CA登记号】813-93-4

【分子式】C₆H₅BiO₇

【分子量】398.08187

【元素组成】C 18.1% H 1.27% Bi 52.5% O 28.13%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VIII)

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2

该中间体在本合成路线中的序号：(VII)

The alkylation of 3-hydroxybenzaldehyde (I) with N-(3-bromopropyl)phthalimide (II) in the presence of NaOMe leads to 3-(phthalimidopropoxy)benzaldehyde (III). The reductive alkylation of piperidine with aldehyde (III) in the presence of formic acid gives N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]phthalimide (IV), which is converted to N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]amine (V) by treatment with 6N HCl. Condensation of (V) with glycolic acid in boiling xylene provides N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-2-hydroxyacetamide (VI), which is complexed with bismuth (+3) citrate (VII) in boiling water.

参考文献中间体

合成目标

【1】 Petkov, O.; Lytakov, G.; Taskov, M.; Savov, E.; Kostev, V.; Tsvetkova, E.; Nikolov, G.; Atanassova, R.; Ivanov, C.; Synthesis, gastroprotective, antisecretory and anti-Helicobacter effect of +[3(3-(1-piperidinylmethyl)phenoxy)propyl]hydroxyacetamide-2-hydroxypropane-1,2,3-tricarboxylate-bismuth(3+) complex (MX1). J Pharm Pharmacol 1996, 3, 3, 297-301.
【2】 N-(3-(3-(1-Piperidinylmethyl)phenoxy)propyl)propenetricarboxylate bismuth (3+) complex and the method for preparation. WO 9509162 .
【3】 Mondeshka, D.; Spassov, G.; Krushkov, I.; Ivanov, C.; Marazova, K.; Roxatidine Bismuth Citrate. Drugs Fut 2000, 25, 5, 462.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10158	Piperidine	110-89-4	C₅H₁₁N	详情	详情
(I)	28537	3-hydroxybenzaldehyde	100-83-4	C₇H₆O₂	详情	详情
(II)	15216	N-(3-Bromopropyl)phthalimide; 2-(3-bromopropyl)-1H-isoindole-1,3(2H)-dione	5460-29-7	C₁₁H₁₀BrNO₂	详情	详情
(III)	35289	3-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propoxy]benzaldehyde		C₁₈H₁₅NO₄	详情	详情
(IV)	35290	2-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-isoindole-1,3(2H)-dione		C₂₃H₂₆N₂O₃	详情	详情
(V)	16105	3-[3-(piperidinomethyl)phenoxy]-1-propanamine; 3-[3-(piperidinomethyl)phenoxy]propylamine		C₁₅H₂₄N₂O	详情	详情
(VI)	29857	2-hydroxy-N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]acetamide		C₁₇H₂₆N₂O₃	详情	详情
(VII)	13855	bismuth(3+) 2-hydroxy-1,2,3-propanetricarboxylate; Bismuth Citrate	813-93-4	C₆H₅BiO₇	详情	详情

Extended Information