6-hydroxy-3,4-dihydro-2(1H)-naphthalenone -Drug Synthesis Database

【结构式】

【分子编号】40937

【品名】6-hydroxy-3,4-dihydro-2(1H)-naphthalenone

【CA登记号】

【分子式】C₁₀H₁₀O₂

【分子量】162.1882

【元素组成】C 74.06% H 6.21% O 19.73%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

Enamine (III), prepared from beta-tetralone (I) by condensation with pyrrolidine (II) in refluxing benzene, was alkylated with bromoacetonitrile to provide, after hydrolytic treatment, keto nitrile (IV). Reductive amination of (IV) with ammonium acetate and NaBH3CN in MeOH furnished the benzo[e]indole tricyclic derivative (V), isolated as the hydrochloride salt. Coupling of (V) with trans-4-[(benzenesulfonamido) methyl]cyclohexanecarboxylic acid (VI) using O-benzotriazol-1-yl-N,N,N’,N’-tetramethyluronium hexafluorophosphate (HBTU) gave amide (VII). This was finally reduced to the corresponding amine employing LiAlH4 in THF.

参考文献中间体

合成目标

【1】 Wilson, S.J.; Dax, S.L.; Nepomuceno, D.H.; McNally, J.J.; Youngman, M.A.; Lovenverg, T.W.; N-(Sulfonamido)alkyl[tetrahydro-1H-benzo[e]indol-2-yl]amines: Potent antagonists of human neuropeptide Y Y5 receptor. Bioorg Med Chem Lett 2000, 10, 3, 213.

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)	40937	6-hydroxy-3,4-dihydro-2(1H)-naphthalenone		C₁₀H₁₀O₂	详情	详情
(II)	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情
(III)	40938	6-(1-pyrrolidinyl)-7,8-dihydro-2-naphthalenol		C₁₄H₁₇NO	详情	详情
(IV)	40939	2-(6-hydroxy-2-oxo-1,2,3,4-tetrahydro-1-naphthalenyl)acetonitrile		C₁₂H₁₁NO₂	详情	详情
(V)	40940	(3aS,9bR)-2-amino-3a,4,5,9b-tetrahydro-1H-benzo[e]indol-7-ol		C₁₂H₁₄N₂O	详情	详情
(VI)	37020	4-[[(phenylsulfonyl)amino]methyl]cyclohexanecarboxylic acid		C₁₄H₁₉NO₄S	详情	详情
(VII)	40941	N-[(3aS,9bR)-7-hydroxy-3a,4,5,9b-tetrahydro-1H-benzo[e]indol-2-yl]-4-[[(phenylsulfonyl)amino]methyl]cyclohexanecarboxamide		C₂₆H₃₁N₃O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Aldol condensation of 3-pyridinecarboxaldehyde (II) with tetralone (I) in the presence of piperidine provided unsaturated ketone (III). This was subjected to reductive amination with ammonium formate and sodium cyanoborohydride to give the cis-aminotetralin (IV). Finally, amine (IV) was coupled with [4-(2-oxo-1-benzimidazolinyl)piperidin-1-yl]acetic acid (V) using HBTU.

参考文献中间体

合成目标

【1】 Lovenberg, T.W.; Dax, S.L.; McNally, J.J.; Wilson, S.; Nepomuceno, D.; Youngman, M.A.; N-acylated alpha-(3-pyridylmethyl)-beta-aminotetralin antagonists of the human neuropeptide Y Y5 receptor. Bioorg Med Chem Lett 2000, 10, 15, 1641.

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)	40937	6-hydroxy-3,4-dihydro-2(1H)-naphthalenone		C₁₀H₁₀O₂	详情	详情
(II)	12849	Nicotinaldehyde; 3-Pyridinecarboxaldehyde	500-22-1	C₆H₅NO	详情	详情
(III)	44719	6-hydroxy-1-[(Z)-3-pyridinylmethylidene]-3,4-dihydro-2-naphthalenone		C₁₆H₁₃NO₂	详情	详情
(IV)	44720	(5R,6S)-6-amino-5-(3-pyridinylmethyl)-5,6,7,8-tetrahydro-2-naphthalenol		C₁₆H₁₈N₂O	详情	详情
(V)	44721	2-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinyl]acetic acid		C₁₄H₁₇N₃O₃	详情	详情

Extended Information