tert-butyl (3R)-3-[3-[(R)-1,3-benzodioxol-5-yl(hydroxy)methyl]-6-butyl-2-pyridinyl]-3-[2-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-4-methoxyphenyl]propanoate -Drug Synthesis Database

【结构式】

【分子编号】38557

【品名】tert-butyl (3R)-3-[3-[(R)-1,3-benzodioxol-5-yl(hydroxy)methyl]-6-butyl-2-pyridinyl]-3-[2-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-4-methoxyphenyl]propanoate

【CA登记号】

【分子式】C₄₁H₅₉NO₇Si

【分子量】706.0075

【元素组成】C 69.75% H 8.42% N 1.98% O 15.86% Si 3.98%

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：(XX)

The cyclization of the intermediate 3-(6-butyl-3-formylpyridin-2-yl)-2(E)-propenoic acid tert-butyl ester (VI) with the chiral auxiliary (XV) by means of AcOH gives the chiral oxazolidine (XVI), which is enantioselectively condensed with the intermediate 3-(2-bromo-5-methoxyphenyl)-2(S)-methyl-1-propanol tert-butyldimethylsilyl ether (XIV) by means of n-BuLi to yield the adduct (XVII). Elimination of the chiral auxiliary with citric acid affords the aldehyde (XVIII), which is treated with 1,3-benzodioxol-5-ylmagnesium bromide (XIX) to provide the corresponding secondary alcohol (XX). Alternatively, the cyclization of the intermediate 3-(6-butyl-3-formylpyidin-2-yl)-2(E)-propenoic acid tert-butyl ester (VI) with the chiral auxiliary (XXI) by means of AcOH gives the chiral oxazolidine (XXII), which is enantioselectively condensed with the intermediate 3-(2-bromo-5-methoxyphenyl)-2(S)-methyl-1-propanol tert-butyldimethylsilyl ether (XIV) by means of n-BuLi to yield the adduct (XXIII). Elimination of the chiral auxiliary with citric acid affords the previously reported aldehyde (XVIII).

参考文献中间体

合成目标

【1】 Song, Z.J.; et al.; Practical asymetric synthesis of an endothelin receptor antagonist. J Org Chem 1999, 64, 26, 9658.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	27564	tert-butyl (E)-3-(6-butyl-3-formyl-2-pyridinyl)-2-propenoate		C₁₇H₂₃NO₃	详情	详情
(XIV)	27567	4-bromo-3-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)phenyl methyl ether		C₁₇H₂₉BrO₂Si	详情	详情
(XV)	38554	(1S,2R)-1-(methylamino)-2,3-dihydro-1H-inden-2-ol		C₁₀H₁₃NO	详情	详情
(XVI)	38555	tert-butyl (E)-3-[6-butyl-3-(3-methyl-2,3-dihydro-1,3-benzoxazol-2-yl)-2-pyridinyl]-2-propenoate		C₂₄H₃₀N₂O₃	详情	详情
(XVII)	38556	tert-butyl (3R)-3-[2-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-4-methoxyphenyl]-3-[6-butyl-3-(3-methyl-2,3-dihydro-1,3-benzoxazol-2-yl)-2-pyridinyl]propanoate		C₄₁H₆₀N₂O₅Si	详情	详情
(XVIII)	27569	tert-butyl (3R)-3-[2-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-4-methoxyphenyl]-3-(6-butyl-3-formyl-2-pyridinyl)propanoate		C₃₄H₅₃NO₅Si	详情	详情
(XIX)	27570	1,3-benzodioxol-5-yl(bromo)magnesium		C₇H₅BrMgO₂	详情	详情
(XX)	38557	tert-butyl (3R)-3-[3-[(R)-1,3-benzodioxol-5-yl(hydroxy)methyl]-6-butyl-2-pyridinyl]-3-[2-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-4-methoxyphenyl]propanoate		C₄₁H₅₉NO₇Si	详情	详情
(XXI)	34409	(1S,2S)-2-(methylamino)-1-phenyl-1-propanol	90-82-4	C₁₀H₁₅NO	详情	详情
(XXII)	27566	tert-butyl (E)-3-[6-butyl-3-[(4S,5S)-3,4-dimethyl-5-phenyl-1,3-oxazolidin-2-yl]-2-pyridinyl]-2-propenoate		C₂₇H₃₆N₂O₃	详情	详情
(XXIII)	27568	tert-butyl (3R)-3-[6-butyl-3-[(4S,5S)-3,4-dimethyl-5-phenyl-1,3-oxazolidin-2-yl]-2-pyridinyl]-3-[2-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-4-methoxyphenyl]propanoate		C₄₄H₆₆N₂O₅Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XX)

The cyclization of (XX) by means of ClPO(OEt)2 and LiHMDS gives the cyclopenta[b]pyridine (XXIV), which is hydrolyzed and desilylated yielding the hydroxyacid (XXV). Finally, the primary alcohol of (XXV) is oxidized with NaClO2, TEMPO and NaClO or with H5IO6/CrO3.

参考文献中间体

合成目标

【1】 Song, Z.J.; et al.; Practical asymetric synthesis of an endothelin receptor antagonist. J Org Chem 1999, 64, 26, 9658.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XX)	38557	tert-butyl (3R)-3-[3-[(R)-1,3-benzodioxol-5-yl(hydroxy)methyl]-6-butyl-2-pyridinyl]-3-[2-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-4-methoxyphenyl]propanoate	C₄₁H₅₉NO₇Si	详情	详情
(XXIV)	38558	tert-butyl (5S,7R)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-[2-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-4-methoxyphenyl]-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate	C₄₁H₅₇NO₆Si	详情	详情
(XXV)	38559	(5S,7R)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-[2-[(2S)-3-hydroxy-2-methylpropyl]-4-methoxyphenyl]-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylic acid	C₃₁H₃₅NO₆	详情	详情

Extended Information