【结 构 式】 |
【分子编号】53389 【品名】3-Phthalimidopropionic acid; Phthalyl-beta-alanine 【CA登记号】3339-73-9 |
【 分 子 式 】C11H9NO4 【 分 子 量 】219.1968 【元素组成】C 60.28% H 4.14% N 6.39% O 29.2% |
合成路线1
该中间体在本合成路线中的序号:(I)Acylation of phenethylamine (III) with acid chloride (II), prepared from phthalimidopropionic acid (I) and SOCl2, gave amide (IV). Subsequent Bischler-Napieralski cyclization of amide (IV) in the presence of POCl3 and P2O5 produced the corresponding dihydroisoquinoline, which was isolated as the hydrochloride salt (V). Catalytic hydrogenation of (V) using PtO2 afforded the tetrahydroisoquinoline (VI). After protection of (VI) as the N-Boc derivative (VII), the primary amine (VIII) was liberated by phthaloyl group hydrazinolysis. Coupling of amine (VIII) with nicotinic acid (IX) employing EDC and HOBt yielded the nicotinamide compound (X). Subsequent acidic cleavage of the Boc protecting group of (X) provided amine (XI), which was finally acylated with 4-butylbenzenesulfonyl chloride (XII) in the presence of resin-bound piperidine to furnish the target sulfonamide.
【1】 Barn, D.R.; et al.; Parallel synthesis and biological activity of a new class of high affinity and selective delta-opioid ligand. Bioorg Med Chem 2001, 9, 10, 2609. |
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) | 53389 | 3-Phthalimidopropionic acid; Phthalyl-beta-alanine | 3339-73-9 | C11H9NO4 | 详情 | 详情 |
(II) | 53390 | 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoyl chloride | n/a | C11H8ClNO3 | 详情 | 详情 |
(III) | 18333 | Phenethylamine; 2-Phenyl-1-ethanamine | 64-04-0 | C8H11N | 详情 | 详情 |
(IV) | 53391 | 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-phenethylpropanamide | n/a | C19H18N2O3 | 详情 | 详情 |
(V) | 53392 | 2-[2-(3,4-dihydro-1-isoquinolinyl)ethyl]-1H-isoindole-1,3(2H)-dione | n/a | C19H16N2O2 | 详情 | 详情 |
(VI) | 53393 | 2-[2-(1,2,3,4-tetrahydro-1-isoquinolinyl)ethyl]-1H-isoindole-1,3(2H)-dione | n/a | C19H18N2O2 | 详情 | 详情 |
(VII) | 53394 | tert-butyl 1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3,4-dihydro-2(1H)-isoquinolinecarboxylate | n/a | C24H26N2O4 | 详情 | 详情 |
(VIII) | 53395 | tert-butyl 1-(2-aminoethyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate | n/a | C16H24N2O2 | 详情 | 详情 |
(IX) | 10752 | Nicotinic acid; Niacin | 59-67-6 | C6H5NO2 | 详情 | 详情 |
(X) | 53396 | tert-butyl 1-{2-[(3-pyridinylcarbonyl)amino]ethyl}-3,4-dihydro-2(1H)-isoquinolinecarboxylate | n/a | C22H27N3O3 | 详情 | 详情 |
(XI) | 53397 | N-[2-(1,2,3,4-tetrahydro-1-isoquinolinyl)ethyl]nicotinamide | n/a | C17H19N3O | 详情 | 详情 |
(XII) | 53398 | 4-n-Butylbenzenesulphonyl chloride | 54997-92-1 | C10H13ClO2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(III)Treatment of beta-alanine (I) with phthalic anhydride (II) in refluxing toluene provides phthalimidopropionic acid (III), which upon cyclocondensation with 2-aminophenol (IV) in hot polyphosphoric acid provides the benzoxazole derivative (V). Hydrazinolysis of phthalimide (V) affords the primary amine (VI), which is finally condensed with pyrazole-1-carboxamidine hydrochloride (VII) in DMF to produce the target guanidine compound.
【1】 López-Tudanca, P.; Labeaga, L.; Innerárity, A.; Alonso-Cires, L.; Tapia, I.; Mosquera, R.; Orjales, A.; Synthesis and pharmacological characterization of a new benzoxazole derivative as a potent 5-HT3 receptor agonist. Bioorg Med Chem 2003, 11, 13, 2709. |
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) | 17022 | beta-Alanine; 3-aminopropionic acid | 107-95-9 | C3H7NO2 | 详情 | 详情 |
(II) | 11900 | 2-Benzofuran-1,3-dione;1,2-Benzenedicarboxylic Anhydride;1,2-BENZENE DICARBOXYLIC ACID ANHYDRIDE;1,2-BENZENEDICARBONIC ACID, ANHYDRIDE;1,3-DIOXOPHTHALAN;1,3-ISOBENZOFURANDIONE;o-phthalic anhydride; Phthalic anhydride | 85-44-9 | C8H4O3 | 详情 | 详情 |
(III) | 53389 | 3-Phthalimidopropionic acid; Phthalyl-beta-alanine | 3339-73-9 | C11H9NO4 | 详情 | 详情 |
(IV) | 18663 | o-aminophenol; 2-aminophenol | 95-55-6 | C6H7NO | 详情 | 详情 |
(V) | 64846 | 2-[2-(1,3-benzoxazol-2-yl)ethyl]-1H-isoindole-1,3(2H)-dione | C17H12N2O3 | 详情 | 详情 | |
(VI) | 64847 | 2-(1,3-benzoxazol-2-yl)-1-ethanamine; 2-(1,3-benzoxazol-2-yl)ethylamine | C9H10N2O | 详情 | 详情 | |
(VII) | 15983 | 1H-pyrazole-1-carboximidamide | 4023-00-1 | C4H6N4 | 详情 | 详情 |