【结 构 式】 |
【分子编号】30045 【品名】(2S)-N-benzyl-3-(4-chlorophenyl)-2-(methylamino)-N-[3-(4-pyridinyl)-1-[2-(4-pyridinyl)ethyl]propyl]propanamide 【CA登记号】 |
【 分 子 式 】C32H35ClN4O 【 分 子 量 】527.10896 【元素组成】C 72.92% H 6.69% Cl 6.73% N 10.63% O 3.04% |
合成路线1
该中间体在本合成路线中的序号:(IX)Condensation of 1,3-acetonedicarboxylic acid (I) with pyridine-4-carboxaldehyde (II) and subsequent acid decarboxylation produced 1,5-dipyridylpentadienone (III), which was reduced to the saturated ketone (IV) by transfer hydrogenation using formic acid and Pd/C. Condensation of (IV) with benzyl amine (V) in benzene with azeotropical removal of water, followed by reduction of the intermediate imine with NaBH4 gave rise to the secondary amine (VI). Coupling of (VI) with N-Boc-N-methyl-L-4-chlorophenylalanine (VII) in the presence of EDC afforded amide (VIII). After Boc deprotection of (VIII) with trifluoroacetic acid, the resulting amine (IX) was coupled with 3,4,5-trimethoxybenzoylformic acid (X) to furnish the title compound.
【1】 Zelle, R.E.; Harding, M.W. (Vertex Pharmaceuticals Inc.); Novel amino acid derivs. with improved multi-drug resistance activity. EP 0797567; JP 1998509151; US 5543423; WO 9615101 . |
【2】 Zelle, R.E. (Vertex Pharmaceuticals Inc.); Methods and compsns. for stimulating neurite growth using cpds. with affinity for FKBP2 in combination with neurotrophic factors. WO 9820891 . |
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) | 15530 | 1,3-Acetonedicarboxylic Acid; 3-Oxopentanedioic acid;3-oxoglutaric acid | 542-05-2 | C5H6O5 | 详情 | 详情 |
(II) | 17203 | 4-Pyridinecarboxaldehyde; isonicotinaldehyde | 872-85-5 | C6H5NO | 详情 | 详情 |
(III) | 30040 | (1E,4E)-1,5-di(4-pyridinyl)-1,4-pentadien-3-one | C15H12N2O | 详情 | 详情 | |
(IV) | 30041 | 1,5-di(4-pyridinyl)-3-pentanone | C15H16N2O | 详情 | 详情 | |
(V) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
(VI) | 30042 | N-benzyl-1,5-di(4-pyridinyl)-3-pentanamine; N-benzyl-N-[3-(4-pyridinyl)-1-[2-(4-pyridinyl)ethyl]propyl]amine | C22H25N3 | 详情 | 详情 | |
(VII) | 30043 | (2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-(4-chlorophenyl)propionic acid | 125324-00-7 | C15H20ClNO4 | 详情 | 详情 |
(VIII) | 30044 | tert-butyl (1S)-2-(benzyl[3-(4-pyridinyl)-1-[2-(4-pyridinyl)ethyl]propyl]amino)-1-(4-chlorobenzyl)-2-oxoethyl(methyl)carbamate | C37H43ClN4O3 | 详情 | 详情 | |
(IX) | 30045 | (2S)-N-benzyl-3-(4-chlorophenyl)-2-(methylamino)-N-[3-(4-pyridinyl)-1-[2-(4-pyridinyl)ethyl]propyl]propanamide | C32H35ClN4O | 详情 | 详情 | |
(X) | 30046 | 2-oxo-2-(3,4,5-trimethoxyphenyl)acetic acid | C11H12O6 | 详情 | 详情 |