【结 构 式】 |
【分子编号】55571 【品名】4-Formylcinnamic acid 【CA登记号】23359-08-2 |
【 分 子 式 】C10H8O3 【 分 子 量 】176.17172 【元素组成】C 68.18% H 4.58% O 27.25% |
合成路线1
该中间体在本合成路线中的序号:(III)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:(I)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 |