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【结 构 式】

【分子编号】65606

【品名】 

【CA登记号】 

【 分 子 式 】C11H12F3NO3

【 分 子 量 】263.2164296

【元素组成】C 50.19% H 4.6% F 21.65% N 5.32% O 18.24%

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:(XXVI)

Two procedures have been reported for the synthesis of the intermediate 2-methyl-2-[5-(trifluoromethyl)pyridin-2-yloxy]propionic acid (I). 2-Chloro-5-(trifluoromethyl)pyridine (XXIII) is coupled with lithium lactate (XXIV) employing NaH in hot DMF to produce the 2-(pyridyloxy)propionic acid (XXV). After esterification of acid (XXV) with trimethylsilyldiazomethane in MeOH/CH2Cl2, the resulting methyl ester is alkylated with iodomethane and sodium hexamethyldisilazide to furnish the (pyridyloxy)isobutyrate (XXVI). Subsequent hydrolysis of methyl ester (XXVI) with NaOH in H2O/MeOH/THF provides the target carboxylic acid intermediate (I) (1). Alternatively, the condensation of 2-hydroxy-5-(trifluoromethyl)pyridine (XXVII) with ethyl 2-bromoisobutyrate (XXVIII) in the presence of cesium carbonate provides the 2-(pyridyloxy)isobutyrate ester (XXIX), which is hydrolyzed to the corresponding carboxylic acid (I) by means of NaOH in acetonitrile/water (2, 3). Scheme 3.

1 Hagmann, W.K., Lin, L.S., Shah, S.K. et al. (Merck & Co., Inc.). Substituted amides. CA 2478183, EP 1496838, JP 2005519958, JP 2006257090, US 2004058820, US 6972295, WO 03077847.
2 Hagmann, W.K., Lin, L.S., Shah, S.K. et al. (Merck & Co., Inc.). Substituted amides active at the cannabinoid-1 receptor. WO 2004048317.
3 Lin, L.S., Lanza, T.J. Jr., Jewell, J.P. et al. Discovery of N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-[[5-(trifluoromethyl)pyridin-2-yl]oxy]propanamide (MK-0364), a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity. J Med Chem 2006, 49(26): 7584-7.
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) 65585 2-Methyl-2-[[5-(Trifluoromethyl)-2-Pyridinyl]Oxy]Propanoic Acid 605680-62-4 C10H10F3NO3 详情 详情
(XXIII) 59113 2-Chloro-5-(trifluoromethyl)pyridine; 5-Trifluoromethyl-2-chloropyridine 52334-81-3 C6H3ClF3N 详情 详情
(XXIV) 65604 Lithium Lactate 16891-53-5 C3H5LiO3 详情 详情
(XXV) 65605     C9H8F3NO3 详情 详情
(XXVI) 65606     C11H12F3NO3 详情 详情
(XXVII) 65607 2-Hydroxy-5-trifluoromethylpyridine; 5-(Trifluoromethyl)pyridin-2-ol 33252-63-0 C6H4F3NO 详情 详情
(XXVIII) 39799 ethyl 2-bromo-2-methylpropanoate 600-00-0 C6H11BrO2 详情 详情
(XXIX) 65608 2-Methyl-2-[[5-(Trifluoromethyl)-2-Pyridinyl]Oxy]-Propanoic Acid Ethyl Ester 913849-17-9 C12H14F3NO3 详情 详情
Extended Information