• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】64941

【品名】2-[4-(trifluoromethyl)phenyl]oxirane

【CA登记号】

【 分 子 式 】C9H7F3O

【 分 子 量 】188.1491896

【元素组成】C 57.45% H 3.75% F 30.29% O 8.5%

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:(II)

The reaction of 4-(trifluoromethyl)styrene (I) with mCPBA in dichloromethane gives the epoxide (II), which is treated with MeONa in methanol to yield the benzyl alcohol (III). The reaction of (III) with MsCl and TEA affords the mesylate (IV), which is condensed with the monoprotected piperazine (V) in refluxing acetonitrile to provide a diastereomeric mixture of compounds (VI) + (VII) that is resolved by flash chromatography. The desired isomer (VII) is deprotected by means of HCl or TFA to give piperazine (VIII), which is condensed with N-Boc-4-piperidone (IX) with simultaneous alkylation by means of Ti(OiPr)4 and Et2Al-CN in refluxing dichloromethane to yield the intermediate (X). The reaction of (X) with MeMgBr in THF affords the methylated compound (XI), which is deprotected by means of TFA to provide the substituted piperidine derivative (XII). Finally, this compound is acylated by means of 4,6-dimethylpyrimidine-5-carbonyl chloride (XIII) and aqueous NaOH in dichloromethane to provide the target compound. (1-3)

1 Imamura, S.; Baba, M.; Ishihara, Y.; Hashiguchi, S.; Kanzaki, N.; Nishimura, O. (Takeda Chemical Industries, Ltd.); Cyclic amide cpds., process for the preparation of the same and uses thereof. EP 1180513; JP 2001011073; WO 0066551 .
2 Neustadt, B.R.; Smith, E.M.; McKittrick, B.A.; McCombie, S.W.; Tagat, J.R.; Clader, J.W.; Vice, S.F.; Baroudy, B.M.; Josien, H.B.; Miller, M.W.; Palani, A.; Steensma, R.; Gilbert, E.; Labroli, M.A. (Schering Corp.); Piperazine derivs. useful as CCR5 antagonists. US 6391865 .
3 Neustadt, B.R.; Smith, E.M.; McKittrick, B.A.; McCombie, S.W.; Tagat, J.R.; Clader, J.W.; Vice, S.F.; Laughlin, M.A.; Baroudy, B.M.; Josien, H.B.; Miller, M.W.; Palani, A.; Steensma, R.; Gilbert, E.; Labroli, M.A. (Schering Corp.); Piperazine derivs. useful as CCR5 antagonists. US 2003069252; US 6689765 .
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) 64940 1-ethenyl-4-(trifluoromethyl)benzene C9H7F3 详情 详情
(II) 64941 2-[4-(trifluoromethyl)phenyl]oxirane C9H7F3O 详情 详情
(III) 64942 2-(methyloxy)-1-[4-(trifluoromethyl)phenyl]-1-ethanol C10H11F3O2 详情 详情
(IV) 64943 2-(methyloxy)-1-[4-(trifluoromethyl)phenyl]ethyl methanesulfonate C11H13F3O4S 详情 详情
(V) 51868 tert-butyl (3S)-3-methyl-1-piperazinecarboxylate C10H20N2O2 详情 详情
(VI) 64944 1,1-dimethylethyl 3-methyl-4-{2-(methyloxy)-1-[4-(trifluoromethyl)phenyl]ethyl}-1-piperazinecarboxylate C20H29F3N2O3 详情 详情
(VII) 64945 1,1-dimethylethyl 3-methyl-4-{2-(methyloxy)-1-[4-(trifluoromethyl)phenyl]ethyl}-1-piperazinecarboxylate C20H29F3N2O3 详情 详情
(VIII) 64946 2-methyl-1-{2-(methyloxy)-1-[4-(trifluoromethyl)phenyl]ethyl}piperazine; methyl 2-(2-methyl-1-piperazinyl)-2-[4-(trifluoromethyl)phenyl]ethyl ether C15H21F3N2O 详情 详情
(IX) 18620 tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone 79099-07-3 C10H17NO3 详情 详情
(X) 64947 1,1-dimethylethyl 4-cyano-4-(3-methyl-4-{2-(methyloxy)-1-[4-(trifluoromethyl)phenyl]ethyl}-1-piperazinyl)-1-piperidinecarboxylate C26H37F3N4O3 详情 详情
(XI) 64948 1,1-dimethylethyl 4-methyl-4-(3-methyl-4-{2-(methyloxy)-1-[4-(trifluoromethyl)phenyl]ethyl}-1-piperazinyl)-1-piperidinecarboxylate C26H40F3N3O3 详情 详情
(XII) 64949 methyl 2-[2-methyl-4-(4-methyl-4-piperidinyl)-1-piperazinyl]-2-[4-(trifluoromethyl)phenyl]ethyl ether; 2-methyl-1-{2-(methyloxy)-1-[4-(trifluoromethyl)phenyl]ethyl}-4-(4-methyl-4-piperidinyl)piperazine C21H32F3N3O 详情 详情
(XIII) 64950 4,6-dimethyl-5-pyrimidinecarbonyl chloride C7H7ClN2O 详情 详情
Extended Information