【结 构 式】 |
【分子编号】45067 【品名】8-chloro-1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid 【CA登记号】 |
【 分 子 式 】C13H8ClF2NO3 【 分 子 量 】299.6609664 【元素组成】C 52.11% H 2.69% Cl 11.83% F 12.68% N 4.67% O 16.02% |
合成路线1
该中间体在本合成路线中的序号:(IX)The synthesis of [14C]-labeled clinafloxacin hydrochloride has been reported: The chlorination of 2,4,5-trifluorobromobenzene (I) with lithium diisopropylamide and hexachlorocyclopentadiene gives 3-chloro-2,4,5-trifluorobromobenzene (II), which is carbonated with 14CO2 and butyllithium in ether yielding 3-chloro-2,4,5-trifluoro-3-chlorobenzoic acid (III). The reaction of (III) with SOCl2 affords the corresponding acyl chloride (IV), which is condensed with the dilithium salt of the malonic acid monoethyl ester (V) to give the benzoylacetate (VI). The reaction of (VI) with acetic anhydride and ethyl orthoformate at 120-30 C yields the ethoxymethylene derivative (VII), which by treatment with cyclopropylamine affords the aminomethylene compound (VIII). The cyclization of (VIII) by means of potassium tert-butoxide in DMSO gives 1-cyclopropyl-8-chloro-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carbox ylic acid (IX), which is condensed with N-[pyrrolidin-3(S)-yl]carbamic acid tert-butyl ester by means of triethylamine in hot DMSO yielding the protected final product (XI). Finally, this compound is deprotected with 12N HCl in THF.
【1】 Huang, C.C.; Ekhato, I.V.; A synthetic approach to carbon-14 labeled anti-bacterial naphthyridine and quinolone carboxylic acids. J Label Compd Radiopharm 1993, 33, 9, 869. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
12263 | Cyclopropylamine; Cyclopropanamine | 765-30-0 | C3H7N | 详情 | 详情 | |
(I) | 11676 | 1-Bromo-2,4,5-trifluorobenzene | 327-52-6 | C6H2BrF3 | 详情 | 详情 |
(II) | 11677 | 1-Bromo-3-chloro-2,4,5-trifluorobenzene | C6HBrClF3 | 详情 | 详情 | |
(III) | 11678 | 3-Chloro-2,4,5-trifluorobenzoic acid | C7H2ClF3O2 | 详情 | 详情 | |
(III) | 45062 | 3-chloro-2,4,5-trifluorobenzoic acid | C7H2ClF3O2 | 详情 | 详情 | |
(IV) | 11679 | 3-Chloro-2,4,5-trifluorobenzoyl chloride | C7HCl2F3O | 详情 | 详情 | |
(IV) | 45063 | 3-chloro-2,4,5-trifluorobenzoyl chloride | C7HCl2F3O | 详情 | 详情 | |
(V) | 11680 | Lithium (1-carboxylato-2-ethoxy-2-oxoethyl)lithium | C5H6Li2O4 | 详情 | 详情 | |
(VI) | 11681 | ethyl 3-(3-chloro-2,4,5-trifluorophenyl)-3-oxopropanoate | 101987-86-4 | C11H8ClF3O3 | 详情 | 详情 |
(VI) | 45064 | ethyl 3-(3-chloro-2,4,5-trifluorophenyl)-3-oxopropanoate | C11H8ClF3O3 | 详情 | 详情 | |
(VII) | 11682 | ethyl (Z)-2-(3-chloro-2,4,5-trifluorobenzoyl)-3-ethoxy-2-propenoate | C14H12ClF3O4 | 详情 | 详情 | |
(VII) | 45065 | ethyl (Z)-2-(3-chloro-2,4,5-trifluorobenzoyl)-3-ethoxy-2-propenoate | C14H12ClF3O4 | 详情 | 详情 | |
(VIII) | 11683 | ethyl (E)-2-(3-chloro-2,4,5-trifluorobenzoyl)-3-(cyclopropylamino)-2-propenoate | C15H13ClF3NO3 | 详情 | 详情 | |
(VIII) | 45066 | ethyl (E)-2-(3-chloro-2,4,5-trifluorobenzoyl)-3-(cyclopropylamino)-2-propenoate | C15H13ClF3NO3 | 详情 | 详情 | |
(IX) | 11684 | 8-Chloro-1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid | 101987-89-7 | C13H8ClF2NO3 | 详情 | 详情 |
(IX) | 45067 | 8-chloro-1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid | C13H8ClF2NO3 | 详情 | 详情 | |
(X) | 11685 | tert-butyl N-[(3S)tetrahydro-1H-pyrrol-3-yl]carbamate | C9H18N2O2 | 详情 | 详情 | |
(XI) | 11686 | 7-[(3S)-3-[(tert-Butoxycarbonyl)amino]tetrahydro-1H-pyrrol-1-yl]-8-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid | C22H25ClFN3O5 | 详情 | 详情 | |
(XI) | 45068 | 7-[(3S)-3-[(tert-butoxycarbonyl)amino]pyrrolidinyl]-8-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid | C22H25ClFN3O5 | 详情 | 详情 |