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Celiprolol hydrochloride, ST-1396, Cordiax, Selectol, Celectol

盐酸塞利洛尔 塞利洛尔 Chemical Name: 3-[3-Acetyl-4-(1,1-dimethylethylamino-2-hydroxypropoxy)phenyl]-1,1-diethylurea hydrochloride
CAS No. 57470-78-7, 56980-93-9 (free base)
项目整合开发状态: Launched-1982
项目研究机构: Aventis Pharma (Originator), Crinos (Not Determined), Nippon Shinyaku (Licensee)
合成路线:The condensation of 3-acetyl-4-hydroxyaniline (I) with N,N-diethylcarbamoyl chloride (II) in pyridine gives the urea (II),which is treated with epichlorohydrin (IV) and NaOH to yield N-[3-acetyl-4-(2,3-epoxypropoxy)phenyl]-N',N'-diethylurea (V).Finally,the epoxy ring of (V) is opened with tert-butylamine (VI).

合成路线:The reaction of 3-acetyl-4-[3-(tert-butylamino)-2-hydroxypropoxy)aniline (VII) with phenyl carbamate (VIII) in pyridine gives the N-[3-acetyl-4-[3-(tert-butylamino)-2-hydroxypropoxy]phenylcarbamic acid phenyl ester (IX),which is tretated with diethylamine (X) in ethanol/water.By reaction of N-[3-acetyl-4-(3-chloro-2-hydroxypropoxy)phenyl]-N',N'-diethylurea (XI) with tert-butylamine (VI).
📌 参考资料/链接:
参考文献标题:4-Ureido-2-acyl phenoxypropanolamine
文献作者:Stormann-Menninger-Lerchenthal,H.; Pittner,H.; Z鰈ss,G.(CL Pharma)
参考来源:DE 2458624; US 4034009

📄 详细内容


合成路线:The reaction of 4-nitrophenol (I) with acetic anhydride in aqueous NaOH gives the corresponding acetate (II),which is submitted to a Fries migration with AlCl3 in nitrobenzene at 140 C to yield the acetophenone (III).The condensation of (III) with epichlorohydrin (IV) by means of K2CO3 affords the adduct (V),which is treated with tert-butylamine (VI) in water to obtain the aminoisopropanol derivative (VII).The reduction of the nitro group of (VII) with H2 over Pd/C in methanol gives the corresponding amino derivative (VIII),which is finally condensed with N,N-diethylcarbamoyl chloride (IX) by means of TEA in THF to yield the target urea.

参考文献标题:A new and improved process for celiprolol hydrochloride
文献作者:Joshi,R.A.; et al.
参考来源:Org Process Res Dev 2001,5(2),176


合成路线:The reaction of D-mannitol (I) with acetone and ZnCl2 gives the diacetonide (II),which is oxidized with Pb(OAc)4 to yield the acetonide of (R)-glyceraldehyde (III).The reduction of (III) with H2 over Pd/C affords the (S)-glycerin acetonide (IV),which is treated with TsCl in pyridine to provide the corresponding tosylate (V).The condensation of (V) with the urea derivative (VI) by means of KOH in DMSO gives the adduct (VII),which is deprotected with HCl in acetone to yield the diol (VIII).Monotosylation of (VIII) with TsCl in pyridine affords the primary tosylate (IX),which is treated with Na in methanol to provide the epoxide (X).Finally this compound is treated with tert-butylamine to furnish the target (R)-enantiomer.

参考文献标题:Absolute configuration and enantiomeric purity of celiprolol
文献作者:Hofer,O.; Schl鰃l,K.
参考来源:Arzneim-Forsch Drug Res 1986,36(8),1157


合成路线:The condensation of 4-ethoxyaniline (II) with N,N-diethylcarbamoyl chloride (II) by means of KHCO3 gives the urea (III),which is acylated with acetyl chloride and AlCl3 to yield N-(3-acetyl-4-hydroxyphenyl)-N',N'-diethylurea (IV).The alkylation of (IV) with epichlorohydrin (V) affords the adduct (VI),which is treated with HBr providing the bromoalcohol (VII).Finally this compound is treated with tert-butylamine to furnish the target urea.

参考文献标题:On the synthesis of the cardioselective beta-adrenergic receptor blocking agent celiprolol
文献作者:Z鰈ss,G.
参考来源:Arzneim-Forsch Drug Res 1983,33(1a),2


合成路线:There are several pathways for the preparation of the title compound according to the patent literature.

参考文献标题:
文献作者:Zoelss,G.; et al.
参考来源:AT 334385


合成路线:There are several pathways for the preparation of the title compound according to the patent literature.

参考文献标题:
文献作者:Zoelss,G.
参考来源:AT 335465


合成路线:There are several pathways for the preparation of the title compound according to the patent literature.

参考文献标题:
文献作者:Zoelss,G.
参考来源:AT 335464


产品链接: CAS No. 57470-78-7››

产品链接: CAS No.56980-93-9››