isopropyl (3S)-3-(1,3-benzodioxol-5-yl)-3-(2-bromo-6-butyl-3-pyridinyl)propanoate -Drug Synthesis Database

【结构式】

【分子编号】27585

【品名】isopropyl (3S)-3-(1,3-benzodioxol-5-yl)-3-(2-bromo-6-butyl-3-pyridinyl)propanoate

【CA登记号】

【分子式】C₂₂H₂₆BrNO₄

【分子量】448.35678

【元素组成】C 58.94% H 5.84% Br 17.82% N 3.12% O 14.27%

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：(XL)

In a related procedure, chiral oxazoline (XXXV) was prepared by condensation of ethyl acetimidate (XXXIII) with (S,S)-thiomicamine (XXXII), followed by O-methylation with MeI and sodium tert-pentoxide. Condensation of the lithium salt of (XXXV) with diethylchlorophosphate at -78 C provided phosphonate (XXXVI), which was submitted to a Horner-Emmons reaction with pyridine aldehyde (XV) to yield the vinyl oxazoline (XXXVII). Conjugate addition of the organolithium reagent (XXXVIII) to (XXXVII) then produced adduct (XXXIX) as the major diastereoisomer. Hydrolysis of the oxazoline of (XXXIX) upon refluxing in isopropyl alcohol with H2SO4 yielded isopropyl ester (XL). Pyridine carboxylate (XLI) was further obtained by carbonylation of (XL) under atmosphere of CO in the presence of bis(diphenylphosphino)ferrocene and palladium diacetate in MeOH.

参考文献中间体

合成目标

【1】 Frey, L.F.; Devine, P.N.; Tschaen, D.M.; Dolling, U.H.; Tillyer, R.D.; Kato, Y. (Banyu Pharmaceutical Co., Ltd.; Merck & Co., Inc.); Stereoselective deoxygenation reaction. EP 0923557; JP 1999514676; WO 9806700 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	27563	2-bromo-6-butylnicotinaldehyde		C₁₀H₁₂BrNO	详情	详情
(XXXII)	27578	(1S,2S)-2-amino-1-[4-(methylsulfanyl)phenyl]-1,3-propanediol		C₁₀H₁₅NO₂S	详情	详情
(XXXIII)	12831	ethyl ethanimidoate	1000-84-6	C₄H₉NO	详情	详情
(XXXIV)	27579	[(4S,5S)-2-methyl-5-[4-(methylsulfanyl)phenyl]-4,5-dihydro-1,3-oxazol-4-yl]methanol		C₁₂H₁₅NO₂S	详情	详情
(XXXV)	27580	(4S,5S)-4-(methoxymethyl)-2-methyl-5-[4-(methylsulfanyl)phenyl]-4,5-dihydro-1,3-oxazole		C₁₃H₁₇NO₂S	详情	详情
(XXXVI)	27581	diethyl [(4S,5S)-4-(methoxymethyl)-5-[4-(methylsulfanyl)phenyl]-4,5-dihydro-1,3-oxazol-2-yl]methylphosphonate		C₁₇H₂₆NO₅PS	详情	详情
(XXXVII)	27582	2-bromo-6-butyl-3-((E)-2-[(4S,5S)-4-(methoxymethyl)-5-[4-(methylsulfanyl)phenyl]-4,5-dihydro-1,3-oxazol-2-yl]ethenyl)pyridine		C₂₃H₂₇BrN₂O₂S	详情	详情
(XXXVIII)	27583	1,3-benzodioxol-5-yllithium		C₇H₅LiO₂	详情	详情
(XXXIX)	27584	[(4S,5S)-2-[(2S)-2-(1,3-benzodioxol-5-yl)-2-(2-bromo-6-butyl-3-pyridinyl)ethyl]-5-[4-(methylsulfanyl)phenyl]-4,5-dihydro-1,3-oxazol-4-yl]methyl methyl ether		C₃₀H₃₃BrN₂O₄S	详情	详情
(XL)	27585	isopropyl (3S)-3-(1,3-benzodioxol-5-yl)-3-(2-bromo-6-butyl-3-pyridinyl)propanoate		C₂₂H₂₆BrNO₄	详情	详情
(XLI)	27586	methyl 3-[(1S)-1-(1,3-benzodioxol-5-yl)-3-isopropoxy-3-oxopropyl]-6-butyl-2-pyridinecarboxylate		C₂₄H₂₉NO₆	详情	详情

Extended Information