【结 构 式】 |
【分子编号】49780 【品名】3-Amino-3-(4-chlorophenyl)propionic acid 【CA登记号】 |
【 分 子 式 】C9H10ClNO2 【 分 子 量 】199.63664 【元素组成】C 54.15% H 5.05% Cl 17.76% N 7.02% O 16.03% |
合成路线1
该中间体在本合成路线中的序号:(II),(V)The beta-amino acid (II) was prepared by Knoevenagel condensation of 4-chlorobenzaldehyde (I) with malonic acid in the presence of ammonium acetate. After protection of the amino group of (II) with Fmoc-Cl, the protected amino acid (III) was attached to the trityl chloride polystyrol resin, yielding the amino acid-bound resin (IV). The Fmoc group of (IV) was then removed using piperidine in DMF to afford (V). N-Fmoc-hydrazine (VI) was carbonylated with phosgene to obtain the oxadiazolone (VII). This was condensed with the amino resin (V) producing adduct (VIII). Deprotection of the Fmoc group of (VIII), followed by coupling with N-Fmoc-3-aminobenzoic acid (IX), furnished (X). After a new deprotection of (X) with piperidine in DMF, the guanidino group was introduced by condensation with N,N'-bis-Boc-1-guanylpyrazole to give (XI). Finally, deprotection and cleavage of the resin adduct (XI) was carried out with trifluoroacetic acid in the presence of triisopropylsilane.
【1】 Sulyok, G.A.G.; et al.; Solid-phase synthesis of a nonpeptide RGD mimetic library: New selective alphavbeta3 integrin antagonists. J Med Chem 2001, 44, 12, 1938. |
【2】 Sulyok, G.; Kessler, H.; Holzemann, G.; Goodman, S.; Gibson, C. (Merck Patent GmbH); Diacylhydrazine derivs.. DE 19932796; WO 0105753 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(II),(V) | 49780 | 3-Amino-3-(4-chlorophenyl)propionic acid | C9H10ClNO2 | 详情 | 详情 | |
(III),(IV) | 49781 | 3-(4-chlorophenyl)-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-beta-alanine | C24H20ClNO4 | 详情 | 详情 | |
(I) | 29029 | 4-chlorobenzaldehyde | 104-88-1 | C7H5ClO | 详情 | 详情 |
(VI) | 49782 | 9-Fluorenylmethyl carbazate; Fmoc-hydrazide | 35661-51-9 | C15H14N2O2 | 详情 | 详情 |
(VII) | 49783 | 5-(9H-fluoren-9-ylmethoxy)-1,3,4-oxadiazol-2(3H)-one | C16H12N2O3 | 详情 | 详情 | |
(VIII) | 49784 | 3-(4-chlorophenyl)-N-([2-[(9H-fluoren-9-ylmethoxy)carbonyl]hydrazino]carbonyl)-beta-alanine | C25H22ClN3O5 | 详情 | 详情 | |
(IX) | 49785 | 3-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]benzoic acid | C22H17NO4 | 详情 | 详情 | |
(X) | 49786 | 3-(4-chlorophenyl)-N-[[2-(3-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]benzoyl)hydrazino]carbonyl]-beta-alanine | C32H27ClN4O6 | 详情 | 详情 | |
(XI) | 49787 | N-([2-[3-([[(tert-butoxycarbonyl)amino][(tert-butoxycarbonyl)imino]methyl]amino)benzoyl]hydrazino]carbonyl)-3-(4-chlorophenyl)-beta-alanine | C28H35ClN6O8 | 详情 | 详情 |