RTI-5989-29, -Drug Synthesis Database

【结构式】

【药物名称】RTI-5989-29

【化学名称】3-(4-Hydroxyphenyl)-N-[1(S)-[4(R)-(3-hydroxyphenyl)-3(R),4-dimethylpiperidin-1-ylmethyl]-2-methylpropyl]propionamide

【CA登记号】

【分子式】C₂₇H₃₈N₂O₃

【分子量】438.61551

【开发单位】Lilly (Originator), National Institute on Drug Abuse (Originator), Research Triangle Institute (Originator)

【药理作用】Treatment of Opioid Dependency, TREATMENT OF POISONING, DRUG ABUSE & DEPENDENCY, Treatment of Substance Dependency, kappa-Opioid Antagonists, mu-Opioid Antagonists

合成路线1

Coupling of (3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (I) with N-Boc-L-valine (II) using benzotriazolyloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) provided amide (III). After deprotection of the Boc group of (III) with trifluoroacetic acid, the resulting valyl amide (IV) was reduced with BH3-Me2S to afford diamine (V). Finally, coupling of (V) with 3-(4-hydroxyphenyl)propionic acid (VI) in the presence of BOP yielded the target compound.

参考文献中间体

【1】 Thomas, J.B.; Fall, M.J.; Cooper, J.B.; Rothman, R.B.; Mascarella, S.W.; Xu, H.; Partilla, J.S.; Dersch, C.M.; McCullough, K.B.; Cantrell, B.E.; Zimmerman, D.M.; Carroll, F.I.; Identification of an opioid kappa receptor subtype-selective N-substituent for (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine. J Med Chem 1998, 41, 26, 5188.

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)	16620	3-[(3R,4R)-3,4-dimethylhexahydro-4-pyridinyl]phenol	119193-19-0	C₁₃H₁₉NO	详情	详情
(II)	19733	(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid		C₁₀H₁₉NO₄	详情	详情
(III)	25688	tert-butyl (1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidinyl]carbonyl]-2-methylpropylcarbamate		C₂₃H₃₆N₂O₄	详情	详情
(IV)	25689	(2S)-2-amino-1-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidinyl]-3-methyl-1-butanone		C₁₈H₂₈N₂O₂	详情	详情
(V)	25690	3-[(3R,4R)-1-[(2S)-2-amino-3-methylbutyl]-3,4-dimethylpiperidinyl]phenol		C₁₈H₃₀N₂O	详情	详情
(VI)	25691	3-(4-hydroxyphenyl)propionic acid	501-97-3	C₉H₁₀O₃	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)