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【结 构 式】 
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【分子编号】35395 【品名】N-[4-isopropyl-2-(methylsulfanyl)phenyl]-4-methyl-6-[5-(2-methylphenyl)-3,6-dihydro-1(2H)-pyridinyl]-2-pyrimidinamine; N-[4-isopropyl-2-(methylsulfanyl)phenyl]-N-[4-methyl-6-[5-(2-methylphenyl)-3,6-dihydro-1(2H)-pyridinyl]-2-pyrimidinyl]amine 【CA登记号】 |
【 分 子 式 】C27H32N4S 【 分 子 量 】444.64404 【元素组成】C 72.93% H 7.25% N 12.6% S 7.21% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The Grignard reaction of 1-(tert-butoxycarbonyl)piperidin-3-one (I) with 2-methylphenylmagnesium bromide (II) in THF gives the tertiary alcohol (III), which is dehydrated with TFA or HCl in dioxane yielding the tetrahydropyridine (IV). The condensation of (IV) with 2,4-dichloro-6-methylpyrimidine (V) by means of DIEA in ethanol affords 2-chloro-6-methyl-4-[3-(2-methylphenyl)-1,2,3,6-tetrahydropyridin-1-yl]pyrimidine (VI), which is further condensed with 4-isopropyl-2-(methylsulfanyl)aniline (VII) by means of DIEA in refluxing ethylene glycol to give the secondary amine (VIII). Finally, this compound is alkylated with ethyl iodide and NaH in DMF.
| 【1】 Chaki, S.; Nakazato, A.; Okubo, T.; Kumagai, T.; Tomisawa, K.; Okuyama, S.; CRF1 receptor antagonists: Aryl-1,2,3,6-tetrahydropyridinopyrimidine derivatives. Symp Med Chem 1998, Abst 1-P-26. |
| 【2】 Okubo, T.; Okuyama, S.; Nakazato, A.; Tomisawa, K.; Aibe, I.; Chaki, S.; Kumagai, T.; Tanaka, H. (Taisho Pharmaceutical Co., Ltd.); 4-Tetrahydropyridylpyrimidine derivs.. EP 0976745; JP 1999228568; WO 9842699 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10925 | Iodoethane;ethyl iod | 75-03-6 | C2H5I | 详情 | 详情 | |
| (I) | 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 |
| (II) | 35391 | bromo(2-methylphenyl)magnesium | C7H7BrMg | 详情 | 详情 | |
| (III) | 35392 | tert-butyl 3-hydroxy-3-(2-methylphenyl)-1-piperidinecarboxylate | C17H25NO3 | 详情 | 详情 | |
| (IV) | 35393 | 5-(2-methylphenyl)-1,2,3,6-tetrahydropyridine | C12H15N | 详情 | 详情 | |
| (V) | 35387 | 2,4-dichloro-6-methylpyrimidine | 5424-21-5 | C5H4Cl2N2 | 详情 | 详情 |
| (VI) | 35394 | 2-chloro-4-methyl-6-[5-(2-methylphenyl)-3,6-dihydro-1(2H)-pyridinyl]pyrimidine | C17H18ClN3 | 详情 | 详情 | |
| (VII) | 35389 | 4-isopropyl-2-(methylsulfanyl)phenylamine; 4-isopropyl-2-(methylsulfanyl)aniline | C10H15NS | 详情 | 详情 | |
| (VIII) | 35395 | N-[4-isopropyl-2-(methylsulfanyl)phenyl]-4-methyl-6-[5-(2-methylphenyl)-3,6-dihydro-1(2H)-pyridinyl]-2-pyrimidinamine; N-[4-isopropyl-2-(methylsulfanyl)phenyl]-N-[4-methyl-6-[5-(2-methylphenyl)-3,6-dihydro-1(2H)-pyridinyl]-2-pyrimidinyl]amine | C27H32N4S | 详情 | 详情 |