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项目整合精选>>>Pramipexole hydrochloride, SND-919, PNU-98528E, SND-919CL2Y(free base), U-98528E(free base), SND-919Y, Mirapexin, Sifrol, Mirapex
Pramipexole hydrochloride, SND-919, PNU-98528E, SND-919CL2Y(free base), U-98528E(free base), SND-919Y, Mirapexin, Sifrol, Mirapex
盐酸普拉克索 (R)-普拉克索 普拉克索杂质DChemical Name: (S)-(-)-2-Amino-6-(propylamino)-4,5,6,7-tetrahydrobenzothiazole dihydrochloride
CAS No. 104632-25-9, 104632-28-2 ((R)-isomer), 104632-27-1 ((R)-isomer, diHCl), 104632-26-0 (free base)
项目整合开发状态: Launched-1997
项目研究机构: Boehringer Ingelheim (Originator), Nippon Boehringer Ingelheim (Originator), National Institute of Mental Health (Not Determined)
合成路线:This compound can be obtained in two related ways:1) The cyclization of 4-acetamidocyclohexanone (I) with thiourea (II) by means of Br2 in hot acetic acid gives 6-acetamido-2-amino-4,5,6,7-tetrahydrobenzothiazole (III),which by hydrolysis with refluxing aqueous HBr yields racemic 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole (racemic IV).Optical resolution with L-(+)-tartaric acid affords the (S)-(-)-isomer (IV),which is finally treated with propionaldehyde and LiBH4.2) The reaction of 4-aminocyclohexanol (V) with phthalic anhydride (VI) in toluene gives the phthalimido derivative (VII),which is oxidized with potassium dichromate - H2SO4 to the corresponding cyclohexanone (VIII).The cyclization of (VIII) with thiourea (II) and Br2 as before affords 2-amino-6-phthalimido-4,5,6,7-tetrahydrobenzothiazole (IX),which is deprotected with hydrazine in refluxing ethanol yielding racemic (IV),already obtained.
📌 参考资料/链接：
参考文献标题:Tetrahydrobenzothiazoles,their preparation and their use as intermediates or as medicines
文献作者:Griss,G.et al.(Dr.Karl Thomae GmbH)
参考来源:AU 8551544; DE 3447075; DE 3508947; EP 0186087; ES 8707513; ES 8707514; ES 8707515; JP 1986155377; US 4731374
📄 详细内容
合成路线:This compound can be obtained in two related ways:1) The cyclization of 4-acetamidocyclohexanone (I) with thiourea (II) by means of Br2 in hot acetic acid gives 6-acetamido-2-amino-4,5,6,7-tetrahydrobenzothiazole (III),which by hydrolysis with refluxing aqueous HBr yields racemic 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole (racemic IV).Optical resolution with L-(+)-tartaric acid affords the (S)-(-)-isomer (IV),which is finally treated with propionaldehyde and LiBH4.2) The reaction of 4-aminocyclohexanol (V) with phthalic anhydride (VI) in toluene gives the phthalimido derivative (VII),which is oxidized with potassium dichromate - H2SO4 to the corresponding cyclohexanone (VIII).The cyclization of (VIII) with thiourea (II) and Br2 as before affords 2-amino-6-phthalimido-4,5,6,7-tetrahydrobenzothiazole (IX),which is deprotected with hydrazine in refluxing ethanol yielding racemic (IV),already obtained.
参考文献标题:J.Dopamine autoreceptor agonists: Resolution and pharmacological activity of 2,6-diaminotetrahydrobenzothiazole and an aminothiazole analogue of apomorphine
文献作者:Schneider,C.S.; Mierau,J.
参考来源:J Med Chem 1987,30(3),494
合成路线:This compound can be obtained in two related ways:1) The cyclization of 4-acetamidocyclohexanone (I) with thiourea (II) by means of Br2 in hot acetic acid gives 6-acetamido-2-amino-4,5,6,7-tetrahydrobenzothiazole (III),which by hydrolysis with refluxing aqueous HBr yields racemic 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole (racemic IV).Optical resolution with L-(+)-tartaric acid affords the (S)-(-)-isomer (IV),which is finally treated with propionaldehyde and LiBH4.2) The reaction of 4-aminocyclohexanol (V) with phthalic anhydride (VI) in toluene gives the phthalimido derivative (VII),which is oxidized with potassium dichromate - H2SO4 to the corresponding cyclohexanone (VIII).The cyclization of (VIII) with thiourea (II) and Br2 as before affords 2-amino-6-phthalimido-4,5,6,7-tetrahydrobenzothiazole (IX),which is deprotected with hydrazine in refluxing ethanol yielding racemic (IV),already obtained.
参考文献标题:Pramipexole Hydrochloride
文献作者:De Angelis,L.
参考来源:Drugs Fut 1992,17(4),291