-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】2-(4-Hydroxy-3-methoxy-5-methylphenyl)-2-(pyridin-3-ylamino)ethylphosphonic acid diethyl ester

【CA登记号】420111-16-6

【分子式】C₁₉H₂₇N₂O₅P

【分子量】394.41124

【开发单位】GlaxoSmithKline (Originator), Ilex Oncology (Originator)

【药理作用】Lipoprotein Disorders, Treatment of , METABOLIC DRUGS, Lipoprotein(a) Lowering Agents

合成路线1

The condensation between 4-hydroxy-3-methoxy-5-methylbenzaldehyde (I) and 3-aminopyridine (II) yields the corresponding benzalimine (III). The phenolic hydroxyl group of (III) is then protected as the silyl ether (IV) by using t-butyldimethylsilyl chloride and imidazole. Condensation of imine (IV) with the lithium derivative of diethyl methylphosphonate (V) affords the beta-amino phosphonate (VI). Finally, desilylation of (VI) with tetrabutylammonium fluoride and acetic acid provides the target phenol.

参考文献中间体

【1】 Phan, H.T.; et al.; Synthesis of a new series of compounds with lipoprotein(a)-lowering activity, Part 3: beta-Substituted-beta-amino-ethylphosphonates. Drugs Fut 2002, 27, Suppl. A.
【2】 Ife, R.J.; Nguyen, L.M.; Bentzen, C.L.; Diep, V.V.; Azoulay, R.; Phan, H.T.; Niesor, E.J. (Ilex Oncology Research-Europe SA); beta-Substd. beta-aminoethyl phosphonates. US 2002111488; WO 0234756 .

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)	43812	1-(6-methoxy-2-naphthyl)-1-ethanone	3900-45-6	C₁₃H₁₂O₂	详情	详情
(II)	33327	3-Pyridinylamine; 3-Aminopyridine; 3-Pyridinamine	462-08-8	C₅H₆N₂	详情	详情
(III)	58411	2-methoxy-6-methyl-4-[(3-pyridinylimino)methyl]phenol		C₁₄H₁₄N₂O₂	详情	详情
(IV)	58412	N-[(E)-(4-{[tert-butyl(dimethyl)silyl]oxy}-3-methoxy-5-methylphenyl)methylidene]-N-(3-pyridinyl)amine; N-[(E)-(4-{[tert-butyl(dimethyl)silyl]oxy}-3-methoxy-5-methylphenyl)methylidene]-3-pyridinamine		C₂₀H₂₈N₂O₂Si	详情	详情
(V)	38496	diethyl methylphosphonate	683-08-9	C₅H₁₃O₃P	详情	详情
(VI)	58413	diethyl 2-(4-{[tert-butyl(dimethyl)silyl]oxy}-3-methoxy-5-methylphenyl)-2-(3-pyridinylamino)ethylphosphonate		C₂₅H₄₁N₂O₅PSi	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)