2-[3-(2-pyridinyl)phenyl]acetic acid -Drug Synthesis Database

【结构式】

【分子编号】50904

【品名】2-[3-(2-pyridinyl)phenyl]acetic acid

【CA登记号】

【分子式】C₁₃H₁₁NO₂

【分子量】213.23588

【元素组成】C 73.23% H 5.2% N 6.57% O 15.01%

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：(XI)

Alkylation of benzyl N-allylcarbamate (I) with 5-bromo-1-pentene (II) in the presence of NaH provides the aza diene derivative (III). Cyclization of (III) under olefin metathesis conditions, employing a ruthenium catalyst, gives rise to the tetrahydroazepine (IV). Oxidation of (IV) with m-chloroperbenzoic acid yields epoxide (V), which is subsequently converted into the trans azido alcohol (VI) upon ring opening with NaN3 and NH4Cl. Azide (VI) is reduced to the corresponding amine (VII) by using 1,3-propanedithiol. Acylation of the racemic trans amino alcohol (VII) by N-Boc-L-leucine (VIII) produces a diastereomeric mixture of amides, which are separated by column chromatography. The desired isomer (IX) is then subjected to catalytic hydrogenolysis of the N-carbobenzoxy group to afford azepine (X). Then, acylation of (X) with 3-(2-pyridyl)phenylacetic acid (XI) furnishes amide (XII).

参考文献中间体

合成目标

【1】 Cummings, M.D.; Veber, D.F.; Yamashita, D.; Ru, Y.; Marquis, R.W. Jr.; Thompson, S.K. (SmithKline Beecham Corp.); Protease inhibitors. EP 1158986; WO 0038687 .

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)	49723	benzyl allylcarbamate		C₁₁H₁₃NO₂	详情	详情
(II)	49724	1-Bromo-4-Pentene; 5-Bromo-1-pentene; 4-Penten-1-yl Bromide	1119-51-3	C₅H₉Br	详情	详情
(III)	49725	benzyl allyl(4-pentenyl)carbamate		C₁₆H₂₁NO₂	详情	详情
(IV)	49726	benzyl 2,3,4,7-tetrahydro-1H-azepine-1-carboxylate		C₁₄H₁₇NO₂	详情	详情
(V)	49727	benzyl 8-oxa-3-azabicyclo[5.1.0]octane-3-carboxylate		C₁₄H₁₇NO₃	详情	详情
(VI)	57657	benzyl (3S,4S)-4-azido-3-hydroxy-1-azepanecarboxylate		C₁₄H₁₈N₄O₃	详情	详情
(VII)	57658	benzyl (3S,4S)-4-amino-3-hydroxy-1-azepanecarboxylate		C₁₄H₂₀N₂O₃	详情	详情
(VIII)	31819	(2R)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid	16937-99-8	C₁₁H₂₁NO₄	详情	详情
(IX)	57659	benzyl (3S,4S)-4-({(2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoyl}amino)-3-hydroxy-1-azepanecarboxylate		C₂₅H₃₉N₃O₆	详情	详情
(X)	57660	tert-butyl (1S)-1-({[(3S,4S)-3-hydroxyazepanyl]amino}carbonyl)-3-methylbutylcarbamate		C₁₇H₃₃N₃O₄	详情	详情
(XI)	50904	2-[3-(2-pyridinyl)phenyl]acetic acid		C₁₃H₁₁NO₂	详情	详情
(XII)	57661	tert-butyl (1S)-1-{[((3S,4S)-3-hydroxy-1-{2-[3-(2-pyridinyl)phenyl]acetyl}azepanyl)amino]carbonyl}-3-methylbutylcarbamate		C₃₀H₄₂N₄O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Palladium-catalyzed coupling of methyl (3-bromophenyl)acetate (I) with 2-pyridyl triflate (II) furnished the pyridylphenylacetate ester (III), which was further hydrolyzed with LiOH to the corresponding carboxylic acid (IV). Coupling of acid (IV) with (3S)-3N-Boc-1,3-diamino-2-butanol (V) using HBTU produced amide (VI). After acid cleavage of the Boc protecting group of (VI), the resulting amine (VII) was coupled with N-Boc-leucine (VIII), yielding adduct (IX). Subsequent acidic deprotection of (IX) provided the intermediate amine (X).

参考文献中间体

合成目标

【1】 Bondinell, W.E.; Desjarlais, R.L.; Yamashita, D.S.; Veber, D.F. (GlaxoSmithKline Inc.); Protease inhibitors. WO 9959526 .

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)	50901	methyl 2-(3-bromophenyl)acetate	150529-73-0	C₉H₉BrO₂	详情	详情
(II)	50902	2-Pyridyl trifluoromethanesulfonate; 2-Pyridyl triflate		C₆H₄F₃NO₃S	详情	详情
(III)	50903	methyl 2-[3-(2-pyridinyl)phenyl]acetate		C₁₄H₁₃NO₂	详情	详情
(IV)	50904	2-[3-(2-pyridinyl)phenyl]acetic acid		C₁₃H₁₁NO₂	详情	详情
(V)	50905	tert-butyl (1S)-3-amino-2-hydroxy-1-methylpropylcarbamate		C₉H₂₀N₂O₃	详情	详情
(VI)	50906	tert-butyl (1S)-2-hydroxy-1-methyl-3-([2-[3-(2-pyridinyl)phenyl]acetyl]amino)propylcarbamate		C₂₂H₂₉N₃O₄	详情	详情
(VII)	50907	N-[(3S)-3-amino-2-hydroxybutyl]-2-[3-(2-pyridinyl)phenyl]acetamide		C₁₇H₂₁N₃O₂	详情	详情
(VIII)	23663	(2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid；N-Boc-L-leucine		C₁₁H₂₁NO₄	详情	详情
(IX)	50908	tert-butyl (1S)-1-([[(1S)-2-hydroxy-1-methyl-3-([2-[3-(2-pyridinyl)phenyl]acetyl]amino)propyl]amino]carbonyl)-3-methylbutylcarbamate		C₂₈H₄₀N₄O₅	详情	详情
(X)	50909	(2S)-2-amino-N-[(1S)-2-hydroxy-1-methyl-3-([2-[3-(2-pyridinyl)phenyl]acetyl]amino)propyl]-4-methylpentanamide		C₂₃H₃₂N₄O₃	详情	详情

Extended Information