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【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%

与该中间体有关的原料药合成路线共 1 条

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
Extended Information