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【结 构 式】 
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【分子编号】58498 【品名】7-chloro-4-oxo-2-(1-pyrrolidinylcarbonyl)-1,4-dihydro-3-quinolinecarboxylic acid 【CA登记号】 |
【 分 子 式 】C15H13ClN2O4 【 分 子 量 】320.732 【元素组成】C 56.17% H 4.09% Cl 11.05% N 8.73% O 19.95% |
合成路线1
该中间体在本合成路线中的序号：(VII)Condensation of methyl 4-chloroanthranilate (I) with dimethyl butynedioate (II), followed by cyclization in the presence of potassium tert-butoxide leads to the quinolone dicarboxylate (III). Partial hydrolysis of diester (III) under basic conditions affords mono-acid (IV), which is converted to acid chloride (V) by treatment with SOCl2. Condensation of acid chloride (V) with pyrrolidine provides the corresponding amide (VI). The methyl ester group of (VI) is subsequently hydrolyzed with NaOH to afford the intermediate acid (VII).
| 【1】 Horchler, C.L.; et al.; Synthesis of 7-chloro-4-hydroxy-2-(3-(aryl/heteroaryl)prop-2-ynyl)1,2,5,10-tetrahydropyridazino[4,5-b]quinoline-1,10-diones (PQD I); potent oral glycine antagonists. 28th Natl Med Chem Symp (June 8 2002, San Diego) 2002, Abst 19. |
| 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) | 49161 | 4-Chloroanthranilic acid methyl ester; Methyl 4-chloroanthranilate; Methyl 2-amino-4-chlorobenzoate; 2-Amino-4-chlorobenzoic acid methyl ester | 5900-58-3 | C8H8ClNO2 | 详情 | 详情 |
| (II) | 24551 | Dimethyl acetylenedicarboxylate; Dimethyl 2-butynedioate;Acetylenedicarboxylic acid dimethyl ester | 762-42-5 | C6H6O4 | 详情 | 详情 |
| (III) | 58494 | dimethyl 7-chloro-4-oxo-1,4-dihydro-2,3-quinolinedicarboxylate | C13H10ClNO5 | 详情 | 详情 | |
| (IV) | 58495 | 7-chloro-3-(methoxycarbonyl)-4-oxo-1,4-dihydro-2-quinolinecarboxylic acid | C12H8ClNO5 | 详情 | 详情 | |
| (V) | 58496 | methyl 7-chloro-2-(chlorocarbonyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C12H7Cl2NO4 | 详情 | 详情 | |
| (VI) | 58497 | methyl 7-chloro-4-oxo-2-(1-pyrrolidinylcarbonyl)-1,4-dihydro-3-quinolinecarboxylate | C16H15ClN2O4 | 详情 | 详情 | |
| (VII) | 58498 | 7-chloro-4-oxo-2-(1-pyrrolidinylcarbonyl)-1,4-dihydro-3-quinolinecarboxylic acid | C15H13ClN2O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)Treatment of 3-butyn-2-ol (VIII) with methanesulfonyl chloride and triethylamine produces the propargyl chloride (IX). This is then condensed with tert-butyl carbazate to yield the Boc-protected propargylhydrazine (X). Acylation of (X) with the quinolonecarboxylic acid (VII) affords hydrazide (XI). Palladium-catalyzed coupling between acetylene (XI) and the aryl halide (XII) produces the arylpropinyl compound (XIII). This is finally cyclized in the presence of methanesulfonic acid to the target pyridazinoquinoline.
| 【1】 Horchler, C.L.; et al.; Synthesis of 7-chloro-4-hydroxy-2-(3-(aryl/heteroaryl)prop-2-ynyl)1,2,5,10-tetrahydropyridazino[4,5-b]quinoline-1,10-diones (PQD I); potent oral glycine antagonists. 28th Natl Med Chem Symp (June 8 2002, San Diego) 2002, Abst 19. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 58498 | 7-chloro-4-oxo-2-(1-pyrrolidinylcarbonyl)-1,4-dihydro-3-quinolinecarboxylic acid | C15H13ClN2O4 | 详情 | 详情 | |
| (VIII) | 58499 | 3-butyn-2-ol; Ethynylmethylcarbinol | 65337-13-5 | C4H6O | 详情 | 详情 |
| (IX) | 58500 | 3-chloro-1-butyne | 21020-24-6 | C4H5Cl | 详情 | 详情 |
| (X) | 58501 | tert-butyl 2-(1-methyl-2-propynyl)-1-hydrazinecarboxylate | C9H16N2O2 | 详情 | 详情 | |
| (XI) | 58502 | tert-butyl 2-{[7-chloro-4-oxo-2-(1-pyrrolidinylcarbonyl)-1,4-dihydro-3-quinolinyl]carbonyl}-2-(1-methyl-2-propynyl)-1-hydrazinecarboxylate | C24H27ClN4O5 | 详情 | 详情 | |
| (XII) | 58503 | 3-iodophenol; m-iodophenol | 626-02-8 | C6H5IO | 详情 | 详情 |
| (XIII) | 58504 | tert-butyl 2-{[7-chloro-4-oxo-2-(1-pyrrolidinylcarbonyl)-1,4-dihydro-3-quinolinyl]carbonyl}-2-[3-(3-hydroxyphenyl)-1-methyl-2-propynyl]-1-hydrazinecarboxylate | C30H31ClN4O6 | 详情 | 详情 |