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【结 构 式】

【分子编号】21720

【品名】3,5-dimethoxybenzaldehyde

【CA登记号】7311-34-4

【 分 子 式 】C9H10O3

【 分 子 量 】166.1766

【元素组成】C 65.05% H 6.07% O 28.88%

与该中间体有关的原料药合成路线共 8 条

合成路线1

该中间体在本合成路线中的序号:(III)

The isoquinoline intermediate (IX) has been synthesized as follows: The reduction of methyl 3,5-dimethoxybenzoate (I) with LiAlH4 gives the benzyl alcohol (II), which is treated with Swern oxidant to yield the benzaldehyde (III). The treatment of (III) with the sequence outlined in the scheme the chiral secondary amine is obtained. The cyclization of (IV) with ammonium formate catalyzed by Pd, followed by a treatment with acetic anhydride and POCl3 afforded the dihydroisoquinoline (V), which is reduced with LiAlH4 to the tetrahydro derivative (VI). Cleavage of the methoxy groups of (VI) with BBr3 affords the dihydroxycompound (VII), which is benzylated with benzyl bromide and Cs2CO3 providing the fully benzylated tetrahydroisoquinoline (VIII). Finally, this compound is iodinated with I2 and Ag2SO4 furnishing the desired isoquinoline intermediate (IX).

1 Hoye, T.R.; et al.; Total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B. J Org Chem 1999, 64, 19, 7184.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
12912 1-(Bromomethyl)benzene; Alpha-bromotoluene 100-39-0 C7H7Br 详情 详情
40727 2-phenyl-2-propanamine; 1-methyl-1-phenylethylamine 585-32-0 C9H13N 详情 详情
(I) 37841 methyl 3,5-dimethoxybenzoate 2150-37-0 C10H12O4 详情 详情
(II) 35424 (3,5-dimethoxyphenyl)methanol 705-76-0 C9H12O3 详情 详情
(III) 21720 3,5-dimethoxybenzaldehyde 7311-34-4 C9H10O3 详情 详情
(IV) 37842 (2R)-1-(3,5-dimethoxyphenyl)-N-(1-methyl-1-phenylethyl)-2-propanamine; N-[(1R)-2-(3,5-dimethoxyphenyl)-1-methylethyl]-N-(1-methyl-1-phenylethyl)amine C20H27NO2 详情 详情
(V) 37843 (3R)-6-methoxy-1,3-dimethyl-3,4-dihydro-8-isoquinolinyl methyl ether; (3R)-6,8-dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline C13H17NO2 详情 详情
(VI) 37844 (1R,3R)-6-methoxy-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl methyl ether; (1R,3R)-6,8-dimethoxy-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline C13H19NO2 详情 详情
(VII) 37845 (1R,3R)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol C11H15NO2 详情 详情
(VIII) 37846 benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline C32H33NO2 详情 详情
(IX) 37847 benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline C32H32INO2 详情 详情

合成路线2

该中间体在本合成路线中的序号:(III)

The isoquinoline intermediate (IX) has been synthesized as follows: The reduction of methyl 3,5-dimethoxybenzoate (I) with LiAlH4 gives the benzyl alcohol (II), which is treated with Swern oxidant to yield the benzaldehyde (III). The treatment of (III) with the sequence outlined in the scheme the chiral secondary amine is obtained. The cyclization of (IV) with ammonium formate catalyzed by Pd, followed by a treatment with acetic anhydride and POCl3 afforded the dihydroisoquinoline (V), which is reduced with LiAlH4 to the tetrahydro derivative (VI). Cleavage of the methoxy groups of (VI) with BBr3 affords the dihydroxycompound (VII), which is benzylated with benzyl bromide and Cs2CO3 providing the fully benzylated tetrahydroisoquinoline (VIII). Finally, this compound is iodinated with I2 and Ag2SO4 furnishing the desired isoquinoline intermediate (IX).

1 Hoye, T.R.; et al.; Total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B. J Org Chem 1999, 64, 19, 7184.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
10039 (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine 3886-69-9 C8H11N 详情 详情
12912 1-(Bromomethyl)benzene; Alpha-bromotoluene 100-39-0 C7H7Br 详情 详情
40727 2-phenyl-2-propanamine; 1-methyl-1-phenylethylamine 585-32-0 C9H13N 详情 详情
(I) 37841 methyl 3,5-dimethoxybenzoate 2150-37-0 C10H12O4 详情 详情
(II) 35424 (3,5-dimethoxyphenyl)methanol 705-76-0 C9H12O3 详情 详情
(III) 21720 3,5-dimethoxybenzaldehyde 7311-34-4 C9H10O3 详情 详情
(IV) 37842 (2R)-1-(3,5-dimethoxyphenyl)-N-(1-methyl-1-phenylethyl)-2-propanamine; N-[(1R)-2-(3,5-dimethoxyphenyl)-1-methylethyl]-N-(1-methyl-1-phenylethyl)amine C20H27NO2 详情 详情
(V) 37843 (3R)-6-methoxy-1,3-dimethyl-3,4-dihydro-8-isoquinolinyl methyl ether; (3R)-6,8-dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline C13H17NO2 详情 详情
(VI) 37844 (1R,3R)-6-methoxy-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl methyl ether; (1R,3R)-6,8-dimethoxy-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline C13H19NO2 详情 详情
(VII) 37845 (1R,3R)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol C11H15NO2 详情 详情
(VIII) 37846 benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline C32H33NO2 详情 详情
(IX) 37847 benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline C32H32INO2 详情 详情

合成路线3

该中间体在本合成路线中的序号:(III)

The isoquinoline intermediate (IX) has been synthesized as follows: The reduction of methyl 3,5-dimethoxybenzoate (I) with LiAlH4 gives the benzyl alcohol (II), which is treated with Swern oxidant to yield the benzaldehyde (III). The treatment of (III) with the sequence outlined in the scheme the chiral secondary amine is obtained. The cyclization of (IV) with ammonium formate catalyzed by Pd, followed by a treatment with acetic anhydride and POCl3 afforded the dihydroisoquinoline (V), which is reduced with LiAlH4 to the tetrahydro derivative (VI). Cleavage of the methoxy groups of (VI) with BBr3 affords the dihydroxycompound (VII), which is benzylated with benzyl bromide and Cs2CO3 providing the fully benzylated tetrahydroisoquinoline (VIII). Finally, this compound is iodinated with I2 and Ag2SO4 furnishing the desired isoquinoline intermediate (IX).

1 Hoye, T.R.; et al.; Total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B. J Org Chem 1999, 64, 19, 7184.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
12912 1-(Bromomethyl)benzene; Alpha-bromotoluene 100-39-0 C7H7Br 详情 详情
40727 2-phenyl-2-propanamine; 1-methyl-1-phenylethylamine 585-32-0 C9H13N 详情 详情
(I) 37841 methyl 3,5-dimethoxybenzoate 2150-37-0 C10H12O4 详情 详情
(II) 35424 (3,5-dimethoxyphenyl)methanol 705-76-0 C9H12O3 详情 详情
(III) 21720 3,5-dimethoxybenzaldehyde 7311-34-4 C9H10O3 详情 详情
(IV) 37842 (2R)-1-(3,5-dimethoxyphenyl)-N-(1-methyl-1-phenylethyl)-2-propanamine; N-[(1R)-2-(3,5-dimethoxyphenyl)-1-methylethyl]-N-(1-methyl-1-phenylethyl)amine C20H27NO2 详情 详情
(V) 37843 (3R)-6-methoxy-1,3-dimethyl-3,4-dihydro-8-isoquinolinyl methyl ether; (3R)-6,8-dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline C13H17NO2 详情 详情
(VI) 37844 (1R,3R)-6-methoxy-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl methyl ether; (1R,3R)-6,8-dimethoxy-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline C13H19NO2 详情 详情
(VII) 37845 (1R,3R)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol C11H15NO2 详情 详情
(VIII) 37846 benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline C32H33NO2 详情 详情
(IX) 37847 benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline C32H32INO2 详情 详情

合成路线4

该中间体在本合成路线中的序号:(III)

The isoquinoline intermediate (IX) has been synthesized as follows: The reduction of methyl 3,5-dimethoxybenzoate (I) with LiAlH4 gives the benzyl alcohol (II), which is treated with Swern oxidant to yield the benzaldehyde (III). The treatment of (III) with the sequence outlined in the scheme the chiral secondary amine is obtained. The cyclization of (IV) with ammonium formate catalyzed by Pd, followed by a treatment with acetic anhydride and POCl3 afforded the dihydroisoquinoline (V), which is reduced with LiAlH4 to the tetrahydro derivative (VI). Cleavage of the methoxy groups of (VI) with BBr3 affords the dihydroxycompound (VII), which is benzylated with benzyl bromide and Cs2CO3 providing the fully benzylated tetrahydroisoquinoline (VIII). Finally, this compound is iodinated with I2 and Ag2SO4 furnishing the desired isoquinoline intermediate (IX).

1 Hoye, T.R.; et al.; Total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B. J Org Chem 1999, 64, 19, 7184.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
12912 1-(Bromomethyl)benzene; Alpha-bromotoluene 100-39-0 C7H7Br 详情 详情
40727 2-phenyl-2-propanamine; 1-methyl-1-phenylethylamine 585-32-0 C9H13N 详情 详情
(I) 37841 methyl 3,5-dimethoxybenzoate 2150-37-0 C10H12O4 详情 详情
(II) 35424 (3,5-dimethoxyphenyl)methanol 705-76-0 C9H12O3 详情 详情
(III) 21720 3,5-dimethoxybenzaldehyde 7311-34-4 C9H10O3 详情 详情
(IV) 37842 (2R)-1-(3,5-dimethoxyphenyl)-N-(1-methyl-1-phenylethyl)-2-propanamine; N-[(1R)-2-(3,5-dimethoxyphenyl)-1-methylethyl]-N-(1-methyl-1-phenylethyl)amine C20H27NO2 详情 详情
(V) 37843 (3R)-6-methoxy-1,3-dimethyl-3,4-dihydro-8-isoquinolinyl methyl ether; (3R)-6,8-dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline C13H17NO2 详情 详情
(VI) 37844 (1R,3R)-6-methoxy-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl methyl ether; (1R,3R)-6,8-dimethoxy-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline C13H19NO2 详情 详情
(VII) 37845 (1R,3R)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol C11H15NO2 详情 详情
(VIII) 37846 benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline C32H33NO2 详情 详情
(IX) 37847 benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline C32H32INO2 详情 详情

合成路线5

该中间体在本合成路线中的序号:(I)

The Horner-Emmons condensation of 3,5-dimethoxybenzaldehyde (I) with triethyl phosphonopropionate (II) gives the cinnamate ester (III), which is hydrolyzed, treated with SOCl2 and condensed with the chiral auxiliary acylsultam (IV) to yield the adduct (V). The enantioselective methylation of (V) with Me2CuLi gives compound (VI) as the major diastereomer. Subsequent hydrolysis of (VI) with LiOH furnishes carboxylic acid (VII). The reduction of (VII) with LiAlH4 gives alcohol (VIII). The reaction of (VIII) with Ts-Cl and pyridine affords the tosylate (IX), which is condensed with butylmagnesium bromide (X) by means of Li2CuCl4 in THF to provide the adduct (XI). The demethylation of (XI) with BBr3 in dichloromethane gives the resorcinol derivative (XII), which is condensed with 4-hydroxy-myrtenyl pivalate (XIII) by means of BF3-Et2O to yield the cannabinoid pivalate ester (XIV). Finally, the reductive cleavage of the ester group of (XIV) with LiAlH4 yields the target cannabinoid.

1 Huffman, J.W.; Liddle, J.; Enantioselective synthesis of 11-hydroxy-(1'S,2'R)-dimethylheptyl-DELTA8-THC, a very potent CB1 agonist. Tetrahedron 2001, 57, 36, 7607.
2 Duncan, S.G. Jr.; Huffman, J.W.; Synthesis and pharmacology of the 1',2'-dimethylheptyl-DELTA8-THC isomers: Exceptionally potent cannabinoids. Bioorg Med Chem Lett 1997, 7, 21, 2799.
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) 21720 3,5-dimethoxybenzaldehyde 7311-34-4 C9H10O3 详情 详情
(II) 18816 ethyl 2-(diethoxyphosphoryl)propanoate 3699-66-9 C9H19O5P 详情 详情
(III) 24400 ethyl (E)-3-(3,5-dimethoxyphenyl)-2-methyl-2-propenoate C14H18O4 详情 详情
(IV) 24401 1,7,7-Trimethylbicyclo[2,2,1]heptane-1',2-sultam; (1S)-(-)-2,10-Camphorsultam C10H17NO2S 详情 详情
(V) 24402 4-[(E)-3-(3,5-dimethoxyphenyl)-2-methyl-2-propenoyl]-10,10-dimethyl-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-3,3-dione C22H29NO5S 详情 详情
(VI) 24403 4-[(2S,3S)-3-(3,5-dimethoxyphenyl)-2-methylbutanoyl]-10,10-dimethyl-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-3,3-dione C23H33NO5S 详情 详情
(VII) 24404 (2S,3S)-3-(3,5-dimethoxyphenyl)-2-methylbutyric acid C13H18O4 详情 详情
(VIII) 24405 (2S,3S)-3-(3,5-dimethoxyphenyl)-2-methyl-1-butanol C13H20O3 详情 详情
(IX) 51421 (2S,3S)-3-(3,5-dimethoxyphenyl)-2-methylbutyl 4-methylbenzenesulfonate C20H26O5S 详情 详情
(X) 42802 bromo(butyl)magnesium 693-03-8 C4H9BrMg 详情 详情
(XI) 51422 3-[(1S,2R)-1,2-dimethylheptyl]-5-methoxyphenyl methyl ether; 1-[(1S,2R)-1,2-dimethylheptyl]-3,5-dimethoxybenzene C17H28O2 详情 详情
(XII) 24406 5-[(1S,2R)-1,2-dimethylheptyl]-1,3-benzenediol C15H24O2 详情 详情
(XIII) 24407 [(1R,5S)-4-hydroxy-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl]methyl pivalate C15H24O3 详情 详情
(XIV) 24408 [(6aR,10aR)-3-[(1S,2R)-1,2-dimethylheptyl]-1-hydroxy-6,6-dimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-9-yl]methyl pivalate C30H46O4 详情 详情

合成路线6

该中间体在本合成路线中的序号:(II)

Title compound was prepared by Claisen Schmidt condensation of 4'-cyclohexylacetophenone (I) with 3,5-dimethoxybenzaldehyde (II) in EtOH using NaOH as the catalyst.

1 Nielsen, S.F.; Christensen, S.B.; Gruciani, G.; Kharazmi, A.; Liljefors, T.; Antileishmanial chalcones: Statistical design, synthesis, and three-dimensional quantitative structure-activity relationship analysis. J Med Chem 1998, 41, 24, 4819.
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) 21719 1-(4-cyclohexylphenyl)-1-ethanone 18594-05-3 C14H18O 详情 详情
(II) 21720 3,5-dimethoxybenzaldehyde 7311-34-4 C9H10O3 详情 详情

合成路线7

该中间体在本合成路线中的序号:(III)

4-Methoxybenzyl bromide (I) is condensed with triphenylphosphine in refluxing toluene to produce the phosphonium salt (II). Subsequent Wittig condensation of (II) with 3,5-dimethoxybenzaldehyde (III) gives rise to a mixture of the title Z-stilbene and its E-isomer (IV), which can be separated by means of flash chromatography.

1 Pettit, G.R.; Grealish, M.P.; Jung, M.K.; Hamel, E.; Pettit, R.K.; Chapuis, J.-C.; Schmidt, J.M.; Antineoplastic agents. 465. Structural modification of resveratrol: Sodium resverastatin phosphate. J Med Chem 2002, 45, 12, 2534.
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) 27490 1-(bromomethyl)-4-methoxybenzene C8H9BrO 详情 详情
(II) 64585 (4-methoxybenzyl)(triphenyl)phosphonium bromide C26H24BrOP 详情 详情
(III) 21720 3,5-dimethoxybenzaldehyde 7311-34-4 C9H10O3 详情 详情
(IV) 62024 4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]phenyl methyl ether; 1,3-dimethoxy-5-[(E)-2-(4-methoxyphenyl)ethenyl]benzene C17H18O3 详情 详情

合成路线8

该中间体在本合成路线中的序号:(II)

Acid-catalyzed condensation of dipyrrolylmethane (I) with 3,5-dimethoxybenzaldehyde (II) gives rise to the porphyrin derivative (III). Subsequent demethylation of the methoxy groups of (III) employing BBr3 affords the tetraphenol compound (IV). Finally, partial reduction of (IV) by means of p-toluenesulfonyl hydrazide in hot pyridine furnishes the title compound (1,2).

1 Bourré, L.; Simmoneaux, G.; Ferrand, Y.; Thibaut, S.; Lajat, Y.; Patrice, T.; Synthesis, and in vitro and in vivo evaluation of a diphenylchlorin sensitizer for photodynamic therapy. J Photochem Photobiol B Biol 2003, 69, 3, 179.
2 Bourre, L.; Patrice, T.; Dihydroporphyrin derivs. and their uses. EP 1305317; FR 2812637; US 2004022734; WO 0210173 .
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) 64350 2-(1H-pyrrol-2-ylmethyl)-1H-pyrrole C9H10N2 详情 详情
(II) 21720 3,5-dimethoxybenzaldehyde 7311-34-4 C9H10O3 详情 详情
(III) 64351 3-[12-[3,5-bis(methyloxy)phenyl]-21,22,23,24-tetraazapentacyclo[16.2.1.1~3,6~.1~8,11~.1~13,16~]tetracosa-1,3(24),4,6,8,10,12,14,16(22),17,19-undecaen-2-yl]-5-(methyloxy)phenyl methyl ether; 2,12-bis[3,5-bis(methyloxy)phenyl]-21,22,23,24-tetraazapentacyclo[16.2.1.1~3,6~.1~8,11~.1~13,16~]tetracosa-1,3,5,7,9,11(23),12,14,16,18(21),19-undecaene C36H30N4O4 详情 详情
(IV) 64352 5-[12-(3,5-dihydroxyphenyl)-21,22,23,24-tetraazapentacyclo[16.2.1.1~3,6~.1~8,11~.1~13,16~]tetracosa-1,3,5,7,9,11(23),12,14,16,18(21),19-undecaen-2-yl]-1,3-benzenediol C32H22N4O4 详情 详情
Extended Information