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【结 构 式】

【分子编号】51941

【品名】2-(5-fluoro-2-methyl-1-[(E)-[4-(methylsulfinyl)phenyl]methylidene]-1H-inden-3-yl)acetic acid

【CA登记号】

【 分 子 式 】C20H17FO3S

【 分 子 量 】356.4175832

【元素组成】C 67.4% H 4.81% F 5.33% O 13.47% S 9%

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:(X)

Condensation of p-fluorobenzaldehyde (I) with propionic anhydride (II) by means of sodium propionate at 140 C affords p-fluoro-alpha-methylcinnamic acid (III), which is then hydrogenated over Pd/C in EtOH to provide p-fluoro-alpha-methylhydrocinnamic acid (IV). Derivative (IV) is subjected to cyclization by treatment with polyphosphoric acid (PPA) to give 6-fluoro-2-methylindanone (V), which is converted into 5-fluoro-2-methylindenyl-3-acetic acid (VII) by first condensation with cyanoacetic acid (VI) by means of acetic acid and ammonium acetate in refluxing toluene, followed by hydrolysis with KOH in hot ethanol. Condensation of derivative (VII) with p-methylthiobenzaldehyde (VIII) by means of sodium methoxide in hot MeOH affords 5-fluoro-2-methyl-1-[p-(methylsulfanyl)benzylidene]-3-indenyl acetic acid (IX), which is then oxidized in MeOH/acetone by means of an aqueous solution of sodium periodate to yield methylsulfinylbenzylidene derivative (X). Finally, the target product is obtained by further oxidation of (X) with H2O2 in the presence of sodium methoxide and sodium bicarbonate in MeOH/acetonitrile at -10 C.

1 Mayle, M.J.; Menander, K.B. (Cell Pathways, Inc.); A method for treating patients with acne by administering a cyclic GMP PDE inhibitor. WO 0044372 .
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) 12337 4-fluorobenzaldehyde 459-57-4 C7H5FO 详情 详情
(II) 20095 propionic anhydride 123-62-6 C6H10O3 详情 详情
(III) 48870 (Z)-3-(4-fluorophenyl)-2-methyl-2-propenoic acid C10H9FO2 详情 详情
(IV) 48871 3-(4-fluorophenyl)-2-methylpropionic acid C10H11FO2 详情 详情
(V) 48872 6-Fluoro-2-methylindanone C10H9FO 详情 详情
(VI) 12591 Cyanoacetic Acid; 2-Cyanoacetic acid 372-09-8 C3H3NO2 详情 详情
(VII) 48874 2-(5-fluoro-2-methyl-1H-inden-3-yl)acetic acid C12H11FO2 详情 详情
(VIII) 18815 4-(methylsulfanyl)benzaldehyde; 4-(methylmercapto)benzaldehyde 3446-89-7 C8H8OS 详情 详情
(IX) 51940 2-(5-fluoro-2-methyl-1-[(E)-[4-(methylsulfanyl)phenyl]methylidene]-1H-inden-3-yl)acetic acid C20H17FO2S 详情 详情
(X) 51941 2-(5-fluoro-2-methyl-1-[(E)-[4-(methylsulfinyl)phenyl]methylidene]-1H-inden-3-yl)acetic acid C20H17FO3S 详情 详情
Extended Information