• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】46515

【品名】methyl (E)-3-(4-formylphenyl)-2-propenoate

【CA登记号】7560-50-1

【 分 子 式 】C11H10O3

【 分 子 量 】190.1986

【元素组成】C 69.46% H 5.3% O 25.24%

与该中间体有关的原料药合成路线共 3 条

合成路线1

该中间体在本合成路线中的序号:(IV)

Reduction of 2-methylindole-3-glyoxylamide (I) with LiAlH4 affords 2-methyltryptamine (II). 4-Formylcinnamic acid (III) is esterified with methanolic HCl, and the resulting aldehyde ester (IV) is reductively aminated with 2-methyltryptamine (II) in the presence of NaBH3CN to give (V). The title hydroxamic acid is then obtained by treatment of ester (V) with aqueous hydroxylamine under basic conditions (1). Scheme 1.

1 Bair, K.W., Green, M.A., Perez, L.B., Sharma, S.K., Sambucetti, L., Versace, R.W., Remiszewski, S.W. (Novartis AG; Novartis Pharma GmbH). Deacetylase inhibitors. EP 1318980, JP 2004509105, WO 0222577.
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) 65332 2-methylindole-3-glyoxylamide   C10H10N2O2 详情 详情
(II) 65333 2-Methylindole-3-ethylamine; 2-(2-Methyl-1H-indol-3-yl)-ethylamine; 3-(2-Aminoethyl)-2-methylindole 2731-06-8 C11H14N2 详情 详情
(III) 55571 4-Formylcinnamic acid 23359-08-2 C10H8O3 详情 详情
(IV) 46515 methyl (E)-3-(4-formylphenyl)-2-propenoate 7560-50-1 C11H10O3 详情 详情
(V) 65334     C22H23N2O2 详情 详情

合成路线2

该中间体在本合成路线中的序号:(III)

Palladium-catalyzed coupling of 4-bromobenzaldehyde (I) with methyl acrylate (II) furnished methyl 4-formylcinnamate (III). After aldehyde protection as the ethylene acetal (IV), ester group reduction using DIBAL in cold CH2Cl2 gave rise to the cinnamyl alcohol (V). O-Alkylation of (V) with ethyl iodide in the presence of NaH produced the corresponding ethyl ether (VI). The acetal protecting group of (VI) was then hydrolyzed with HCl to yield aldehyde (VII).

2 Zhang, C.; Mjalli, A.M.M. (Ontogen Corp.); Imidazole derivs. as MDR modulators. EP 0999835; US 5840721; WO 9902155 .
1 Dixon, R.; Zhang, C.; Sarshar, S.; Mjalli, A.M.M.; Rodarte, J.C.; Moran, E.J.; Benbatoul, K.D.; Krane, S.; 2,4,5-Trisubstituted imidazoles: Novel nontoxic modulators of P-glycoprotein mediated multidrug resistance. Part 2. Bioorg Med Chem Lett 2000, 10, 23, 2603.
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) 22231 4-Bromobenzaldehyde 1122-91-4 C7H5BrO 详情 详情
(II) 14156 methyl acrylate 96-33-3 C4H6O2 详情 详情
(III) 46515 methyl (E)-3-(4-formylphenyl)-2-propenoate 7560-50-1 C11H10O3 详情 详情
(IV) 46516 methyl (E)-3-[4-(1,3-dioxolan-2-yl)phenyl]-2-propenoate C13H14O4 详情 详情
(V) 46517 (E)-3-[4-(1,3-dioxolan-2-yl)phenyl]-2-propen-1-ol C12H14O3 详情 详情
(VI) 46518 (E)-3-[4-(1,3-dioxolan-2-yl)phenyl]-2-propenyl ethyl ether; 2-[4-[(E)-3-ethoxy-1-propenyl]phenyl]-1,3-dioxolane C14H18O3 详情 详情
(VII) 46519 4-[(E)-3-ethoxy-1-propenyl]benzaldehyde C12H14O2 详情 详情

合成路线3

该中间体在本合成路线中的序号:(II)

The esterification of 4-formylcinnamic acid (I) with methanol and HCl gives the methyl ester (II), which can be obtained by Heck coupling of 4-bromobenzaldehyde (III) with methyl acrylate (IV). The reductocondensation of (II) with tryptamine (V) by means of NaBH(OAc)3 in dichloroethane yields the secondary amine (VI), which is alkylated with 2-(tert-butyldimethylsilyloxy)ethyl bromide (VII) by means of DIEA in DMSO to afford the tertiary amine (VIII). The reaction of the methyl ester group of (VIII) with KOH and hydroxylamine in methanol provides the silylated hydroxamic acid (IX), which is finally deprotected with TFA in water.

1 Perez, L.B.; Remiszewski, S.; Sambucetti, L.; et al.; Discovery and SAR of NVP-LAQ824, a novel histone deacetylase inhibitor with in vitro and in vivo antitumor activity. Proc Am Assoc Cancer Res 2002, 43, Abst 3671.
2 Bair, K.W.; Versace, R.W.; Green, M.A.; Remiszewski, S.W.; Perez, L.B.; Sambucetti, L.; Sharma, S.K. (Novartis AG; Novartis-Erfindungen VmbH); Deacetylase inhibitors. WO 0222577 .
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) 55571 4-Formylcinnamic acid 23359-08-2 C10H8O3 详情 详情
(II) 46515 methyl (E)-3-(4-formylphenyl)-2-propenoate 7560-50-1 C11H10O3 详情 详情
(III) 22231 4-Bromobenzaldehyde 1122-91-4 C7H5BrO 详情 详情
(IV) 14156 methyl acrylate 96-33-3 C4H6O2 详情 详情
(V) 40537 Tryptamine; 2-(1H-Indol-3-yl)-1-ethanamine; 2-(1H-Indol-3-yl)ethylamine 61-54-1 C10H12N2 详情 详情
(VI) 55572 methyl 3-[4-({[2-(1H-indol-3-yl)ethyl]amino}methyl)phenyl]-2-propenoate C21H22N2O2 详情 详情
(VII) 55573 2-Bromoethoxy-t-butyldimethylsilane 86864-60-0 C8H19BrOSi 详情 详情
(VIII) 55574   C29H40N2O3Si 详情 详情
(IX) 55575 3-[4-({(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)[2-(1H-indol-3-yl)ethyl]amino}methyl)phenyl]-N-hydroxy-2-propenamide C28H39N3O3Si 详情 详情
Extended Information