藥物詳細合成路線

Name	Ritanserin;R-55667;Tiserton
Chemical Name	6-[2-[4-[Bis(p-fluorophenyl)methylene]piperidino]ethyl]-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one
CAS	87051-43-2
Related CAS
Formula	C27H25F2N3OS
Structure
Formula Weight	477.5806
Stage	III 期臨床
Company	Janssen (Originator)
Activity/Mechanism	Antidepressants, Antipsychotic Drugs, Anxiolytics, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, Treatment of Alcohol Dependency, TREATMENT OF POISONING, DRUG ABUSE & DEPENDENCY, Treatment of Substance Dependency, 5-HT2A Antagonists
Syn. Route	1

Route 1 the grignard condensation of ethyl 1-benzyl-piperidine-4-carboxylate (i) with 4-fluorophenylmagnesium bromide (ii) in thf gives a-bis(4-fluorophenyl)-1-benzylpiperidine-4-methanol (iii), which is dehydrated with hcl in refluxing acetic acid yielding 1-benzyl-4-[bis(4 fluorophenyl)methylene]piperidine (iv). elimination of the benzyl group of (iv) by hydrogenation with h2 over rhodium/carbon in methanol affords 4-[bis(4 fluorophenyl)metlylene] piperidine (v), which is finally condensed with 6-(2-chloroethyl)-7-methyl 5h thiazolo[3,2-a]pyrimidin-5-one (vi) by means of na2co3 and ki lo refluxing 4-methyl-2-pentanone. compound (vi) is obtained by cyclocondensation of 2-thiazolylamine (vii) with 3 acetyl 4,5 dihydro-2(3h)furanone (viii) by means of aqueous concentrated hcl in refluxing toluene. List of intermediates No. 2-[(e)-(dimethylamino)methylidene]-1-(3-methoxyphenyl)-1,3-butanedione (ii) methyl 3-(1,3-benzodioxol-5-yl)-2-[(4-methylcyclohexyl)carbonyl]-4-nitrobutanoate (i) methyl 3-(1,3-benzodioxol-5-yl)-5-(4-methylcyclohexyl)-3,4-dihydro-2h-pyrrole-4-carboxylate (iii) 5-amino-1,3-oxazole-4-carbonitrile (iv) methyl trimethoxymethyl ether; tetramethoxymethane (v) 4-cyano-5-[(dimethoxymethylene)amino]-1,3-oxazole (vi) n-propylurea (viii) Reference 1:     kennis, l.e.j.; mertens, j.c.; vandenberk, j. (janssen pharmaceutica nv); novel ((bis(aryl)methylene)-1-piperidinyl)alkyl-pyrimidinones. ep 0110435; es 8601965; us 4485107 . Reference 2:     prous, j.; castaner, j.; ritanserin. drugs fut 1986, 11, 5, 391.

來源:藥化網

作者:藥化小編

摘要:本文合成路線介紹的是藥物中文名利坦色林；英文名Ritanserin;R-55667;Tiserton；CAS[87051-43-2]

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