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【结 构 式】

【分子编号】62030

【品名】(4S)-4-(3-cyanophenyl)-5-oxo-2-(trifluoromethyl)-1,4,5,6,7,8-hexahydro-3-quinolinecarboxylic acid

【CA登记号】

【 分 子 式 】C18H13F3N2O3

【 分 子 量 】362.3081096

【元素组成】C 59.67% H 3.62% F 15.73% N 7.73% O 13.25%

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:(IX)

The reaction of trifluoroacetoacetic acid ethyl ester (I) with (?)-isoborneol (II) at 130 C gives the corresponding isobornyl ester (III), which is condensed with cyclohexane-1,3-dione (IV) and 3-cyanobenzaldehyde (V) by means of ammonium acetate in refluxing ethanol to yield the octahydroquinolone (VI). The hydrolysis of the ester group of (VI), with simultaneous dehydration by means of TsOH in refluxing toluene affords 4-(3-cyanophenyl)-5-oxo-2-(trifluoromethyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxylic acid (VII) as a racemic mixture. Optical resolution of (VII) through the diastereomeric salt with 1(S)-phenylethylamine (VIII) in toluene/butanol provides the desired isomer (IX), which is finally decarboxylated in N-methyl-2-pyrrolidone at 210 C to furnish the target hexahydroquinolone.

1 Ashworth, I.; Hopes, P.; Levin, D.; Patel, I.; Salloo, R.; An asymmetric synthesis of a 4-substituted-1,4-dihydropyridine. Tetrahedron Lett 2002, 43, 28, 4931.
2 Warawa, J.E.; Ohnmacht, C.J. Jr.; Trainor, D.A.; Hulsizer, J.M. (AstraZeneca plc); Quinolone deriv. for treatment of urinary incontinence. EP 0755382; JP 1997512254; WO 9528388 .
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) 62025 propyl 4,4,4-trifluoro-3-oxobutanoate C7H9F3O3 详情 详情
(II) 62026 (1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol C10H18O 详情 详情
(III) 62027 (1R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl 4,4,4-trifluoro-3-oxobutanoate C14H19F3O3 详情 详情
(IV) 11244 1,3-Cyclohexanedione 504-02-9 C6H8O2 详情 详情
(V) 13245 3-Formylbenzonitrile; 3-Cyanobenzaldehyde 24964-64-5 C8H5NO 详情 详情
(VI) 62028 (1R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl 4-(3-cyanophenyl)-2-hydroxy-5-oxo-2-(trifluoromethyl)-1,2,3,4,5,6,7,8-octahydro-3-quinolinecarboxylate C28H31F3N2O4 详情 详情
(VII) 62029 4-(3-cyanophenyl)-5-oxo-2-(trifluoromethyl)-1,4,5,6,7,8-hexahydro-3-quinolinecarboxylic acid C18H13F3N2O3 详情 详情
(VIII) 10039 (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine 3886-69-9 C8H11N 详情 详情
(IX) 62030 (4S)-4-(3-cyanophenyl)-5-oxo-2-(trifluoromethyl)-1,4,5,6,7,8-hexahydro-3-quinolinecarboxylic acid C18H13F3N2O3 详情 详情
Extended Information