4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butanal -Drug Synthesis Database

【结构式】

【分子编号】21620

【品名】4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butanal

【CA登记号】

【分子式】C₁₂H₁₁NO₃

【分子量】217.22428

【元素组成】C 66.35% H 5.1% N 6.45% O 22.1%

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：(II)

Reductive condensation of tetrahydroisoquinoline (I) with 4-phthalimidobutyraldehyde (II) in the presence of sodium triacetoxy borohydride yielded the phthalimidobutyl isoquinoline (III). O-Demethylation of (III) was then accomplished by conversion to the hydrochloride salt, followed by treatment with BBr3 in CH2Cl2 yielding (IV). Reaction of the resulting 7-hydroxy derivative (IV) with trifluoromethanesulfonic anhydride in pyridine afforded triflate (V). Subsequent treatment of (V) with hydrazine hydrate in EtOH removed the phthalimido group, and the resulting amine (VI) was finally coupled with 3-(3-indolyl)propenoic acid (VII) in the presence of EDC and HOBt to give the target amide.

参考文献中间体

合成目标

【1】 Austin, N.E.; et al.; Novel 1,2,3,4-tetrahydroisoquinolines with high affinity and selectivity for the dopamine D3 receptor. Bioorg Med Chem Lett 1999, 9, 2, 179.

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)	21619	7-methoxy-1,2,3,4-tetrahydroisoquinoline; methyl 1,2,3,4-tetrahydro-7-isoquinolinyl ether		C₁₀H₁₃NO	详情	详情
(II)	21620	4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butanal		C₁₂H₁₁NO₃	详情	详情
(III)	21621	2-[4-[7-methoxy-3,4-dihydro-2(1H)-isoquinolinyl]butyl]-1H-isoindole-1,3(2H)-dione		C₂₂H₂₄N₂O₃	详情	详情
(IV)	21622	2-[4-[7-hydroxy-3,4-dihydro-2(1H)-isoquinolinyl]butyl]-1H-isoindole-1,3(2H)-dione		C₂₁H₂₂N₂O₃	详情	详情
(V)	21623	2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butyl]-1,2,3,4-tetrahydro-7-isoquinolinyl trifluoromethanesulfonate		C₂₂H₂₁F₃N₂O₅S	详情	详情
(VI)	21624	2-(4-aminobutyl)-1,2,3,4-tetrahydro-7-isoquinolinyl trifluoromethanesulfonate		C₁₄H₁₉F₃N₂O₃S	详情	详情
(VII)	21625	trans-3-(3-Indolyl)-2-propenoic acid; trans-Indole-3-acrylic acid; trans-beta-Indoleacrylic acid; Indole-3-acrylic acid; 3-(3-Indolyl)acrylic acid; (E)-3-(1H-indol-3-yl)-2-propenoic acid	29953-71-7	C₁₁H₉NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

4-Aminobutyraldehyde diethyl acetal (I) was treated with N-(ethoxycarbonyl)phthalimide (II) in THF to produce the phthalimido acetal (III), which was hydrolyzed to aldehyde (IV) with HCl in aqueous THF. Subsequent reductive alkylation of 7-methoxy-1,2,3,4-tetrahydroisoquinoline (V) with (IV) in the presence of sodium triacetoxyborohydride provided (VI). After conversion to the hydrochloride salt, the methyl ether of (VI) was cleaved using BBr3 in CH2Cl2 to give the phenol (VII), which was treated with trifluoromethanesulfonic anhydride in pyridine to afford triflate (VIII). The phthalimido group of (VIII) was then removed with ethanolic hydrazine and the resulting primary amine (IX) was finally coupled with 3-(3-indolyl)acrylic acid (X) in the presence of EDC and HOBt to yield the target amide.

参考文献中间体

合成目标

【1】 Nash, D.J.; Stemp, G. (SmithKline Beecham plc); Tetrahydroisoquinoline derivs. and their pharmaceutical use. EP 0922035; WO 9806699 .

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)	23323	4,4-diethoxybutylamine; 4,4-diethoxy-1-butanamine	6346-09-4	C₈H₁₉NO₂	详情	详情
(II)	10293	methyl (2R)-2-amino-3-(2-chloro-4-quinolinyl)propanoate		C₁₃H₁₃ClN₂O₂	详情	详情
(III)	23325	2-(4,4-diethoxybutyl)-1H-isoindole-1,3(2H)-dione		C₁₆H₂₁NO₄	详情	详情
(IV)	21620	4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butanal		C₁₂H₁₁NO₃	详情	详情
(V)	21619	7-methoxy-1,2,3,4-tetrahydroisoquinoline; methyl 1,2,3,4-tetrahydro-7-isoquinolinyl ether		C₁₀H₁₃NO	详情	详情
(VI)	21621	2-[4-[7-methoxy-3,4-dihydro-2(1H)-isoquinolinyl]butyl]-1H-isoindole-1,3(2H)-dione		C₂₂H₂₄N₂O₃	详情	详情
(VII)	21622	2-[4-[7-hydroxy-3,4-dihydro-2(1H)-isoquinolinyl]butyl]-1H-isoindole-1,3(2H)-dione		C₂₁H₂₂N₂O₃	详情	详情
(VIII)	21623	2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butyl]-1,2,3,4-tetrahydro-7-isoquinolinyl trifluoromethanesulfonate		C₂₂H₂₁F₃N₂O₅S	详情	详情
(IX)	21624	2-(4-aminobutyl)-1,2,3,4-tetrahydro-7-isoquinolinyl trifluoromethanesulfonate		C₁₄H₁₉F₃N₂O₃S	详情	详情
(X)	21625	trans-3-(3-Indolyl)-2-propenoic acid; trans-Indole-3-acrylic acid; trans-beta-Indoleacrylic acid; Indole-3-acrylic acid; 3-(3-Indolyl)acrylic acid; (E)-3-(1H-indol-3-yl)-2-propenoic acid	29953-71-7	C₁₁H₉NO₂	详情	详情

Extended Information