3-fluoro-4-[(1E,3E)-5-oxo-1,3-pentadienyl]benzonitrile -Drug Synthesis Database

【结构式】

【分子编号】45515

【品名】3-fluoro-4-[(1E,3E)-5-oxo-1,3-pentadienyl]benzonitrile

【CA登记号】

【分子式】C₁₂H₈FNO

【分子量】201.2000632

【元素组成】C 71.64% H 4.01% F 9.44% N 6.96% O 7.95%

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：(VI)

Benzylic bromination of 3-fluoro-4-methylbenzaldehyde (I) using N-bromosuccinimide afforded bromide (II), which was converted to phosphonate (III) by reaction with triethyl phosphite. Horner-Emmons condensation of phosphonate (III) with monoprotected fumaraldehyde (IV) produced the diene acetal (V), which was then hydrolyzed to aldehyde (VI) with aqueous HCl.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; del Fresno, M.; Rabasseda, X.; CS-758. Drugs Fut 2003, 28, 3, 217.
【2】 Nakamura, Y.; Konosu, T.; Oida, S.; et al.; Synthesis and in vitro antifungal activities of novel triazole antifungal agent CS-758. Chem Pharm Bull 2001, 49, 12, 1647.
【4】 Mori, M.; Oida, S.; Uchida, T.; Nakagawa, A.; Kounosu, T.; Ohya, T. (Sankyo Co., Ltd.); Triazole antifungal agents. JP 2002161035 .
【5】 Mori, M.; Oida, S.; Konosu, T.; Uchida, T.; Ohya, S.; Nakagawa, A. (Sankyo Co., Ltd.); Triazole derivs. having antifungal activity. EP 1083175; JP 2001348384; JP 2002114782; US 6337403; US 6391903 .
【3】 Oida, S.; Mori, M.; nakamura, Y.; Habuki, S.; Kuwahara, S.; Somada, A.; Harada, Y.; Uchida, T.; Konosu, T.; R-120758, a novel triazole antifungal agent: Synthesis and structure-activity relationship. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1087.

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)	45510	3-fluoro-4-methylbenzonitrile	170572-49-3	C₈H₆FN	详情	详情
(II)	45511	4-(bromomethyl)-3-fluorobenzonitrile		C₈H₅BrFN	详情	详情
(III)	45512	diethyl 4-cyano-2-fluorobenzylphosphonate		C₁₂H₁₅FNO₃P	详情	详情
(IV)	45513	(E)-4,4-dimethoxy-2-butenal	4093-49-6	C₆H₁₀O₃	详情	详情
(V)	45514	4-[(1E,3E)-5,5-dimethoxy-1,3-pentadienyl]-3-fluorobenzonitrile		C₁₄H₁₄FNO₂	详情	详情
(VI)	45515	3-fluoro-4-[(1E,3E)-5-oxo-1,3-pentadienyl]benzonitrile		C₁₂H₈FNO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Addition of the thiol liberated from thioester (VII) in the presence of NaOMe to the chiral epoxide (VIII) afforded thioether (IX). Acid hydrolysis of the acetal function of (IX) yielded diol (X). Then, acetalization of diol (IX) with aldehyde (XI) furnished the title compound.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; del Fresno, M.; Rabasseda, X.; CS-758. Drugs Fut 2003, 28, 3, 217.
【2】 Nakamura, Y.; Konosu, T.; Oida, S.; et al.; Synthesis and in vitro antifungal activities of novel triazole antifungal agent CS-758. Chem Pharm Bull 2001, 49, 12, 1647.
【4】 Tajima, Y.; Oida, S.; Konosu, T.; et al.; Synthesis and antifungal activities of R-102557 and related dioxane-triazole derivatives. Chem Pharm Bull 2000, 48, 5, 694.
【5】 Oida, S.; Tanaka, T.; Tajima, Y.; Konosu, T.; Somada, A.; Miyaoka, T.; Yasuda, H. (Sankyo Co., Ltd.); Triazole antifungal agent. EP 0841327; JP 1996333350; US 5977152; WO 9631491 .
【6】 Mori, M.; Oida, S.; Uchida, T.; Nakagawa, A.; Kounosu, T.; Ohya, T. (Sankyo Co., Ltd.); Triazole antifungal agents. JP 2002161035 .
【3】 Oida, S.; Mori, M.; nakamura, Y.; Habuki, S.; Kuwahara, S.; Somada, A.; Harada, Y.; Uchida, T.; Konosu, T.; R-120758, a novel triazole antifungal agent: Synthesis and structure-activity relationship. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1087.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	45515	3-fluoro-4-[(1E,3E)-5-oxo-1,3-pentadienyl]benzonitrile	C₁₂H₈FNO	详情	详情
(VII)	41336	S-(2-phenyl-1,3-dioxan-5-yl) ethanethioate	C₁₂H₁₄O₃S	详情	详情
(VIII)	13114	1-[[(2S,3S)-2-(2,4-Difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole	C₁₂H₁₁F₂N₃O	详情	详情
(IX)	41337	(2R,3R)-2-(2,4-difluorophenyl)-3-[(2-phenyl-1,3-dioxan-5-yl)sulfanyl]-1-(1H-1,2,4-triazol-1-yl)-2-butanol	C₂₂H₂₃F₂N₃O₃S	详情	详情
(X)	41338	2-[[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]sulfanyl]-1,3-propanediol	C₁₅H₁₉F₂N₃O₃S	详情	详情

Extended Information