【结 构 式】 |
【分子编号】33795 【品名】methyl 6-[bis(5-fluoro-2-methylbenzoyl)amino]nicotinate 【CA登记号】 |
【 分 子 式 】C23H18F2N2O4 【 分 子 量 】424.4038064 【元素组成】C 65.09% H 4.27% F 8.95% N 6.6% O 15.08% |
合成路线1
该中间体在本合成路线中的序号:(VIIIa)Alkylation of pyrrole-2-carboxaldehyde (II) with 2-nitrobenzyl chloride (I) in the presence of NaH afforded the N-benzyl pyrrole (III). Subsequent reductive ring closure of (III) by hydrogenation over Pd/C produced the pyrrolobenzodiazepine (IV). Acid-catalyzed esterification of 6-aminonicotinic acid (V) with either methanol or ethanol provided the corresponding esters (VIa) or (VIb). Further coupling of (VIa) or (VIb) with two equivalents of 5-fluoro-2-methylbenzoyl chloride (VII) gave rise to imide (VIII). Simultaneous hydrolysis of ester function and one benzoyl group of (VIIIa-b) with NaOH furnished acid (IX), which was then converted to the corresponding acid chloride (X) employing either thionyl chloride or oxalyl chloride. Finally, coupling of acid chloride (X) with amine (IV) in the presence of Et3N yielded the target amide.
【1】 Albright, J.D.; Venkatesan, A.M.; Dusza, J.P.; Sum, F.W. (American Cyanamid Co.); Tricyclic benzazepine vasopressin antagonists. US 5700796; WO 9749708 . |
【2】 Burgoyne, D.L.; Shen, Y.; Langlands, J.M.; Rogers, C.; Chau, J.H.-L.; Piers, E.; Salari, H. (InflaZyme Pharmaceuticals Ltd.); 6,7-Oxygenated steroids and uses related thereto. US 6046185; WO 9802450 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VIa) | 12114 | methyl 6-aminonicotinate | C7H8N2O2 | 详情 | 详情 | |
(VIb) | 33794 | ethyl 6-aminonicotinate | C8H10N2O2 | 详情 | 详情 | |
(VIIIa) | 33795 | methyl 6-[bis(5-fluoro-2-methylbenzoyl)amino]nicotinate | C23H18F2N2O4 | 详情 | 详情 | |
(VIIIb) | 33814 | ethyl 6-[bis(5-fluoro-2-methylbenzoyl)amino]nicotinate | C24H20F2N2O4 | 详情 | 详情 | |
(I) | 33792 | 1-(chloromethyl)-2-nitrobenzene | 612-23-7 | C7H6ClNO2 | 详情 | 详情 |
(II) | 21081 | Pyrrole-2-carbaldehyde; 1H-pyrrole-2-carbaldehyde | 1003-29-8 | C5H5NO | 详情 | 详情 |
(III) | 21083 | 1-(2-nitrobenzyl)-1H-pyrrole-2-carbaldehyde; N-(2-Nitrobenzyl)pyrrole-2-carboxaldehyde | 22162-51-2 | C12H10N2O3 | 详情 | 详情 |
(IV) | 21084 | 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine | 22162-53-4 | C12H12N2 | 详情 | 详情 |
(V) | 33793 | 6-aminonicotinic acid | 3167-49-5 | C6H6N2O2 | 详情 | 详情 |
(VII) | 26677 | 5-fluoro-2-methylbenzoyl chloride | C8H6ClFO | 详情 | 详情 | |
(IX) | 33796 | 6-[(5-fluoro-2-methylbenzoyl)amino]nicotinic acid | C14H11FN2O3 | 详情 | 详情 | |
(X) | 33797 | 6-[(5-fluoro-2-methylbenzoyl)amino]nicotinoyl chloride | C14H10ClFN2O2 | 详情 | 详情 |