【结 构 式】 |
【分子编号】59793 【品名】(3S,4R)-4-ethyl-3-piperidinamine; (3S,4R)-4-ethylpiperidinylamine 【CA登记号】 |
【 分 子 式 】C7H16N2 【 分 子 量 】128.21752 【元素组成】C 65.57% H 12.58% N 21.85% |
合成路线1
该中间体在本合成路线中的序号:(XII)Metalation of 1-bromo-2,4-difluorobenzene (I) by means of LDA, followed by treatment with tert-butyl hydroperoxide gave rise to phenol (II), which was further converted to methyl ether (III) by alkylation with iodomethane and K2CO3. Lithium halogen exchange of (III) with n-butyllithium, and subsequent quenching with CO2 produced 3-methoxy-2,4-difluorobenzoic acid (IV). After activation of (IV) as the acid chloride (V), condensation with the lithium derivative of monoethyl malonate (A) led to the benzoyl acetate ester (VI). The benzoyl ethoxyacrylate (VII), obtained by condensation of ketoester (VI) with triethyl orthoformate, was then reacted with cyclopropylamine (VIII) to afford enamine (IX). This was cyclized to the quinolone compound (X) upon treatment with NaH in THF. Acidic hydrolysis of ester (X) gave a keto acid, which was subsequently converted to the boron chelate (XI) by treatment with boron trifluoride etherate. Fluoride displacement of quinolone (XI) with the amino piperidine (XII) produced the piperidino quinolone (XIII). The boron difluoride complex of (XIII) was finally removed by means of triethylamine in boiling EtOH.
【1】 Hu, X.E.; Gray, J.L.; Almstead, J.-I.K.; Ledoussal, B. (The Procter & Gamble Co.); Antimicrobial quinolones, their compsns. and uses. EP 1015445; WO 9914214 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 15086 | 3-ethoxy-3-oxopropionic acid | 1071-46-1 | C5H8O4 | 详情 | 详情 |
(I) | 15488 | 1-bromo-2,4-difluorobenzene | 348-57-2 | C6H3BrF2 | 详情 | 详情 |
(II) | 34648 | 3-bromo-2,6-difluorophenol | 221220-99-1 | C6H3BrF2O | 详情 | 详情 |
(III) | 34649 | 3-bromo-2,6-difluorophenyl methyl ether; 1-bromo-2,4-difluoro-3-methoxybenzene | 221221-00-7 | C7H5BrF2O | 详情 | 详情 |
(IV) | 30621 | 2,4-difluoro-3-methoxybenzoic acid | 178974-97-5 | C8H6F2O3 | 详情 | 详情 |
(V) | 34650 | 2,4-difluoro-3-methoxybenzoyl chloride | C8H5ClF2O2 | 详情 | 详情 | |
(VI) | 34651 | ethyl 3-(2,4-difluoro-3-methoxyphenyl)-3-oxopropanoate | C12H12F2O4 | 详情 | 详情 | |
(VII) | 34652 | ethyl (Z)-2-(2,4-difluoro-3-methoxybenzoyl)-3-ethoxy-2-propenoate | C15H16F2O5 | 详情 | 详情 | |
(VIII) | 12263 | Cyclopropylamine; Cyclopropanamine | 765-30-0 | C3H7N | 详情 | 详情 |
(IX) | 34653 | ethyl (Z)-3-(cyclopropylamino)-2-(2,4-difluoro-3-methoxybenzoyl)-2-propenoate | C16H17F2NO4 | 详情 | 详情 | |
(X) | 34654 | ethyl 1-cyclopropyl-7-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C16H16FNO4 | 详情 | 详情 | |
(XI) | 59792 | 1-cyclopropyl-3-{[(difluoroboryl)oxy]carbonyl}-7-fluoro-8-methoxy-4(1H)-quinolinone | C14H11BF3NO4 | 详情 | 详情 | |
(XII) | 59793 | (3S,4R)-4-ethyl-3-piperidinamine; (3S,4R)-4-ethylpiperidinylamine | C7H16N2 | 详情 | 详情 | |
(XIII) | 59794 | 7-[(3S,4R)-3-amino-4-ethylpiperidinyl]-1-cyclopropyl-3-{[(difluoroboryl)oxy]carbonyl}-8-methoxy-4(1H)-quinolinone | C21H26BF2N3O4 | 详情 | 详情 |