2-[2-cyano-5-(4-pyridinylmethoxy)phenoxy]-2-(2-methylphenyl)acetic acid -Drug Synthesis Database

【结构式】

【分子编号】38986

【品名】2-[2-cyano-5-(4-pyridinylmethoxy)phenoxy]-2-(2-methylphenyl)acetic acid

【CA登记号】

【分子式】C₂₂H₁₈N₂O₄

【分子量】374.396

【元素组成】C 70.58% H 4.85% N 7.48% O 17.09%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(V)

The alkylation of 2-fluoro-4-hydroxybenzonitrile (I) with 4-picolyl chloride (II) afforded ether (III). This was coupled with (R,S)-2-hydroxy-2-(2-methylphenyl)acetic acid (IV) in the presence of NaH in DMSO to produce the racemic adduct (V). Resolution of (V) was then achieved by fractional crystallization of the diastereoisomeric salts with (-)-ephedrine to furnish the desired (S)-enantiomer, which was finally isolated as the corresponding sodium salt.

参考文献中间体

合成目标

【1】 Astles, P.C.; Brown, T.J.; Halley, F.; et al.; Selective ETA antagonists. 5. Discovery and structure-activity relationships of phenoxyphenylacetic acid derivatives. J Med Chem 2000, 43, 5, 900.
【2】 Porter, B.; Astles, P.C.; Bridge, A.W.; McLay, I.M.; Van Sickle, A.P.; Walsh, R.J.A.; McCarthy, C.; Morley, A.D.; Halley, F.; Harris, N.V.; Majid, T.N.; Smith, C. (Rhône-Poulenc Rorer Ltd.); Substd. phenyl cpds. as endothelin antagonists. US 6048893; US 6124343; WO 9622978 .

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)	20094	2,4-dihydroxybenzaldehyde	95-01-2	C₇H₆O₃	详情	详情
(II)	10844	4-(Chloromethyl)pyridine	10445-91-7	C₆H₆ClN	详情	详情
(III)	38985	2-fluoro-4-(4-pyridinylmethoxy)benzonitrile		C₁₃H₉FN₂O	详情	详情
(IV)	38977	2-hydroxy-2-(2-methylphenyl)acetic acid		C₉H₁₀O₃	详情	详情
(V)	38986	2-[2-cyano-5-(4-pyridinylmethoxy)phenoxy]-2-(2-methylphenyl)acetic acid		C₂₂H₁₈N₂O₄	详情	详情

Extended Information