Tamsulosin hydrochloride, Amsulosin hydrochloride, Y-617, YM-12617-1, LY-253351, YM-617, EU-617, Josir, Omix, Harnal, Flomax, Alna, Flomax MR, Omic, Omnic, Pradif, -Drug Synthesis Database

【结构式】

【药物名称】Tamsulosin hydrochloride, Amsulosin hydrochloride, Y-617, YM-12617-1, LY-253351, YM-617, EU-617, Josir, Omix, Harnal, Flomax, Alna, Flomax MR, Omic, Omnic, Pradif

【化学名称】(-)-(R)-5-[2-[2-(2-Ethoxyphenoxy)ethylamino]propyl]-2-methoxybenzenesulfonamide hydrochloride

【CA登记号】106463-17-6, 106133-20-4 (free base), 80223-99-0 (racemate)

【分子式】C₂₀H₂₉ClN₂O₅S

【分子量】444.98153

【开发单位】Yamanouchi (Originator), Boehringer Ingelheim (Licensee), Abbott (Comarketer), National Institutes of Health (Codevelopment)

【药理作用】Benign Prostatic Hyperplasia Therapy, RENAL-UROLOGIC DRUGS, Urologic Drugs, alpha1-Adrenoceptor Antagonists

合成路线1 合成路线2

合成路线1

A new synthesis of YM-12617-1, the active R-isomer of YM-12617, has been described: The reductocondensation of 1-(4-methoxyphenyl)-2-propanone (I) with R-1-phenylethylamine (II) gives regioselectively the secondary amine (III) as the HCl salt, which by sulfonation with chlorosulfonic acid and treatment with NH4OH yields (R,R)-2-methoxy-5-[2-(1-phenylethylamino)propyl]benzenesulfonamide (IV). Eliminating the protecting group by hydrogenation, the free amine hydrochloride (V) is obtained, which is finally submitted to a reductocondensation with 2-(2-ethoxyphenoxy)acetaldehyde (VI) by means of sodium borohydride in methanol, and treated with HCl in ether.

参考文献中间体

【1】 Hunden, D.C.; Wheller, W.J.; Schmiegel, K.K.; The synthesis of the 14C and 2H-isotopomers of (R)-N-[2-(2'-ethoxyphenoxy)-ethyl]-N-2-[3-(4'-methoxy-3'-sulfonamido)-phenyl]-propylamine hydrochloride, an alpha1-adrenoreceptor antagonist. J Label Compd Radiopharm 1989, 26, 2, 171.

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)	10038	4-Methoxyphenylacetone; 1-(4-Methoxyphenyl)acetone	122-84-9	C₁₀H₁₂O₂	详情	详情
(II)	10039	(1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine	3886-69-9	C₈H₁₁N	详情	详情
(III)	10040	(2R)-1-(4-Methoxyphenyl)-N-[(1R)-1-phenylethyl]-2-propanamine; N-[(1R)-2-(4-Methoxyphenyl)-1-methylethyl]-N-[(1R)-1-phenylethyl]amine		C₁₈H₂₃NO	详情	详情
(IV)	10041	2-Methoxy-5-((2R)-2-[[(1R)-1-phenylethyl]amino]propyl)benzenesulfonamide		C₁₈H₂₄N₂O₃S	详情	详情
(V)	10042	5-[(2R)-2-Aminopropyl]-2-methoxybenzenesulfonamide	112101-81-2	C₁₀H₁₆N₂O₃S	详情	详情
(VI)	10043	2-(2-Ethoxyphenoxy)acetaldehyde	103181-55-1	C₁₀H₁₂O₃	详情	详情

合成路线2

The condensation of 2-methoxy-5-(2-bromopropionyl)benzenesulfonamide (I) with N-benzyl-2-(2 ethoxyphenoxy)ethylamine (II) in refluxing butanone gives the tertiary amine (III), which is reduced with sodium in ethanol to the alcohol (IV). Debenzylation of (IV) with H2 over Pd/C in methanol affords the hydroxyamine (V), which by reaction with SOCl2 in acetonitrile is converted to the corresponding chloro derivative (VI). Finally, this compound is dechlorinated by hydrogenolysis with H2 over Pd/C in methanol.

参考文献中间体

【1】 Niigata, K.; Fujikura, T. (Yamanouchi Pharmaceutical Co., Ltd.); Sulfamoyl-substd. phenethylamine derivs., their preparation, and pharmaceutical compsns., containing them. EP 0034432; US 4373106; US 5447958 .
【2】 Fujikura, T.; et al. (Yamanouchi Pharmaceutical Co., Ltd.); Phenylethanolamine derivatives. DE 2843016; ES 474149; ES 481549; FR 2405931; GB 2006772 .
【3】 Castaner, J.; Mannhold, R.; YM-12617. Drugs Fut 1986, 11, 4, 293.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	24025	5-(2-bromopropanoyl)-2-methoxybenzenesulfonamide	C₁₀H₁₂BrNO₄S	详情	详情
(II)	24026	N-benzyl-2-(2-ethoxyphenoxy)-1-ethanamine	C₁₇H₂₁NO₂	详情	详情
(III)	24027	5-(2-[benzyl[2-(2-ethoxyphenoxy)ethyl]amino]propanoyl)-2-methoxybenzenesulfonamide	C₂₇H₃₂N₂O₆S	详情	详情
(IV)	24028	5-(2-[benzyl[2-(2-ethoxyphenoxy)ethyl]amino]-1-hydroxypropyl)-2-methoxybenzenesulfonamide	C₂₇H₃₄N₂O₆S	详情	详情
(V)	24029	5-(2-[[2-(2-ethoxyphenoxy)ethyl]amino]-1-hydroxypropyl)-2-methoxybenzenesulfonamide	C₂₀H₂₈N₂O₆S	详情	详情
(VI)	24030	5-(1-chloro-2-[[2-(2-ethoxyphenoxy)ethyl]amino]propyl)-2-methoxybenzenesulfonamide	C₂₀H₂₇ClN₂O₅S	详情	详情

Extended Information