【药物名称】Oxaprotiline hydrochloride(Rec INNM, USAN), C-49802-B-Ba
化学结构式(Chemical Structure):
参考文献No.67237
标题:C-49802-B-Ba and CGP-6085A
作者:Casta馿r, J.
来源:Drugs Fut 1978,3(6),429
合成路线图解说明:

The reaction of 9-chlorocarbonylmethyl-9,10-dihydro-9,10-ethanoanthracene (I) with the aldehyde (II) with trimethyloxosulfonium iodide by means of NaH in DMSO gives 9-(2-epoxypropyl)-9,10-dihydro-9,10-ethanoanthracene (IX), which is then treated with methylamine in refluxing ethanol.

合成路线图解说明:

The reduction of from 9-chlorocarbonylmethyl-9,10-dihydro-9,10-ethanoanthracene (I) with H2 over Pd/C poisoned with quinoline - sulfur in xylene gives 9,10-dihydro-9,10-ethano-9-anthrylacetaldehyde (II), which is condensed with HCN by means of triethylamine in methylene chloride yielding 9-(2-cyano-2-hydroxyethyl)-9,10-dihydro-9,10-ethanoanthracene (III). The reduction of (III) with LiAlH4 in refluxing THF affords 9-(2-hydroxy-3-aminopropyl)-9,10-dihydro-9,10-ethanoanthracene (IV), which is cyclized with formaldehyde in formic acid at 90 C to give 9-[(3-methyl-5-oxazolidinyl)methyl]-9,10-dihydro-9,10-ethanoanthracene (V). Finally, this compound is hydrolyzed with hot hydrochloric acid. The cyclization of the amine (IV) with phosgene by means of NaOH in dioxane-toluene gives 5-(9,10-hydro-9,10-ethano-9-anthrylmethyl)oxazolidin-2-one (VI), which is reduced with LiAlH4 in refluxing THF.

合成路线图解说明:

Tosylation of the amine (IV) with tosyl chloride in pyridine gives N-(p-toluenesulfonyl)-9-(2-hydroxy-3-aminopropyl)-9,10-dihydro-9,10-ethanoanthracene (VII), which is methylated with diazomethane in ether yielding the corresponding N-methyl derivative (VIII). Finally, this compound is detosylated by treating with LiAlH4 in refluxing THF.

合成路线图解说明:

By autoclaving ethylene with 9-(2-hydroxy-3-methylaminopropyl)anthracene (X).

参考文献No.800586
标题:Amines and processes for their manufacture
作者:Wilhelm, M.; et al.
来源:DE 2207097; ES 400022; FR 2126353; GB 1378241
合成路线图解说明:

The reaction of 9-chlorocarbonylmethyl-9,10-dihydro-9,10-ethanoanthracene (I) with the aldehyde (II) with trimethyloxosulfonium iodide by means of NaH in DMSO gives 9-(2-epoxypropyl)-9,10-dihydro-9,10-ethanoanthracene (IX), which is then treated with methylamine in refluxing ethanol.

合成路线图解说明:

The reduction of from 9-chlorocarbonylmethyl-9,10-dihydro-9,10-ethanoanthracene (I) with H2 over Pd/C poisoned with quinoline - sulfur in xylene gives 9,10-dihydro-9,10-ethano-9-anthrylacetaldehyde (II), which is condensed with HCN by means of triethylamine in methylene chloride yielding 9-(2-cyano-2-hydroxyethyl)-9,10-dihydro-9,10-ethanoanthracene (III). The reduction of (III) with LiAlH4 in refluxing THF affords 9-(2-hydroxy-3-aminopropyl)-9,10-dihydro-9,10-ethanoanthracene (IV), which is cyclized with formaldehyde in formic acid at 90 C to give 9-[(3-methyl-5-oxazolidinyl)methyl]-9,10-dihydro-9,10-ethanoanthracene (V). Finally, this compound is hydrolyzed with hot hydrochloric acid. The cyclization of the amine (IV) with phosgene by means of NaOH in dioxane-toluene gives 5-(9,10-hydro-9,10-ethano-9-anthrylmethyl)oxazolidin-2-one (VI), which is reduced with LiAlH4 in refluxing THF.

合成路线图解说明:

Tosylation of the amine (IV) with tosyl chloride in pyridine gives N-(p-toluenesulfonyl)-9-(2-hydroxy-3-aminopropyl)-9,10-dihydro-9,10-ethanoanthracene (VII), which is methylated with diazomethane in ether yielding the corresponding N-methyl derivative (VIII). Finally, this compound is detosylated by treating with LiAlH4 in refluxing THF.

参考文献No.800587
标题:Verfahren zur Herstellung neuer 9-(2-Hydroxy3-Aminopropyl-9,10-dihydro-9,10-鋘thanoanthracene
作者:Wilhelm, M.; et al.
来源:CH 566293
合成路线图解说明:

The reduction of from 9-chlorocarbonylmethyl-9,10-dihydro-9,10-ethanoanthracene (I) with H2 over Pd/C poisoned with quinoline - sulfur in xylene gives 9,10-dihydro-9,10-ethano-9-anthrylacetaldehyde (II), which is condensed with HCN by means of triethylamine in methylene chloride yielding 9-(2-cyano-2-hydroxyethyl)-9,10-dihydro-9,10-ethanoanthracene (III). The reduction of (III) with LiAlH4 in refluxing THF affords 9-(2-hydroxy-3-aminopropyl)-9,10-dihydro-9,10-ethanoanthracene (IV), which is cyclized with formaldehyde in formic acid at 90 C to give 9-[(3-methyl-5-oxazolidinyl)methyl]-9,10-dihydro-9,10-ethanoanthracene (V). Finally, this compound is hydrolyzed with hot hydrochloric acid. The cyclization of the amine (IV) with phosgene by means of NaOH in dioxane-toluene gives 5-(9,10-hydro-9,10-ethano-9-anthrylmethyl)oxazolidin-2-one (VI), which is reduced with LiAlH4 in refluxing THF.

参考文献No.800588
标题:Verfahren zur Herstellung neuer 9-(2-Hydroxy3-Aminopropyl-9,10-dihydro-9,10-鋘thanoanthracene
作者:Wilhelm, M.; et al.
来源:CH 558774
合成路线图解说明:

The reduction of from 9-chlorocarbonylmethyl-9,10-dihydro-9,10-ethanoanthracene (I) with H2 over Pd/C poisoned with quinoline - sulfur in xylene gives 9,10-dihydro-9,10-ethano-9-anthrylacetaldehyde (II), which is condensed with HCN by means of triethylamine in methylene chloride yielding 9-(2-cyano-2-hydroxyethyl)-9,10-dihydro-9,10-ethanoanthracene (III). The reduction of (III) with LiAlH4 in refluxing THF affords 9-(2-hydroxy-3-aminopropyl)-9,10-dihydro-9,10-ethanoanthracene (IV), which is cyclized with formaldehyde in formic acid at 90 C to give 9-[(3-methyl-5-oxazolidinyl)methyl]-9,10-dihydro-9,10-ethanoanthracene (V). Finally, this compound is hydrolyzed with hot hydrochloric acid. The cyclization of the amine (IV) with phosgene by means of NaOH in dioxane-toluene gives 5-(9,10-hydro-9,10-ethano-9-anthrylmethyl)oxazolidin-2-one (VI), which is reduced with LiAlH4 in refluxing THF.

合成路线图解说明:

By autoclaving ethylene with 9-(2-hydroxy-3-methylaminopropyl)anthracene (X).

参考文献No.800589
标题:Verfahren zur Herstellung neuer 9-(2-Hydroxy3-Aminopropyl-9,10-dihydro-9,10-鋘thanoanthracene
作者:Wilhelm, M.; et al.
来源:CH 563960
合成路线图解说明:

The reduction of from 9-chlorocarbonylmethyl-9,10-dihydro-9,10-ethanoanthracene (I) with H2 over Pd/C poisoned with quinoline - sulfur in xylene gives 9,10-dihydro-9,10-ethano-9-anthrylacetaldehyde (II), which is condensed with HCN by means of triethylamine in methylene chloride yielding 9-(2-cyano-2-hydroxyethyl)-9,10-dihydro-9,10-ethanoanthracene (III). The reduction of (III) with LiAlH4 in refluxing THF affords 9-(2-hydroxy-3-aminopropyl)-9,10-dihydro-9,10-ethanoanthracene (IV), which is cyclized with formaldehyde in formic acid at 90 C to give 9-[(3-methyl-5-oxazolidinyl)methyl]-9,10-dihydro-9,10-ethanoanthracene (V). Finally, this compound is hydrolyzed with hot hydrochloric acid. The cyclization of the amine (IV) with phosgene by means of NaOH in dioxane-toluene gives 5-(9,10-hydro-9,10-ethano-9-anthrylmethyl)oxazolidin-2-one (VI), which is reduced with LiAlH4 in refluxing THF.

合成路线图解说明:

Tosylation of the amine (IV) with tosyl chloride in pyridine gives N-(p-toluenesulfonyl)-9-(2-hydroxy-3-aminopropyl)-9,10-dihydro-9,10-ethanoanthracene (VII), which is methylated with diazomethane in ether yielding the corresponding N-methyl derivative (VIII). Finally, this compound is detosylated by treating with LiAlH4 in refluxing THF.

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