2,4-dichloro-6-methylpyrimidine -Drug Synthesis Database

【结构式】

【分子编号】35387

【品名】2,4-dichloro-6-methylpyrimidine

【CA登记号】5424-21-5

【分子式】C₅H₄Cl₂N₂

【分子量】163.00564

【元素组成】C 36.84% H 2.47% Cl 43.5% N 17.19%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

The Grignard reaction of 1-(tert-butoxycarbonyl)piperidin-4-one (I) with 3-fluorophenylmagnesium 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-4-[4-(3-fluorophenyl)-1,2,3,6-tetrahydropyridin-1-yl]-6-methylpyrimidine (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.

参考文献中间体

合成目标

【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.; Tanaka, H.; Chaki, S.; Okuyama, S.; Tomisawa, K.; Kumagai, T.; Nakazato, A.; Design, synthesis and structure-affinity relationships of 4-methylidenepiperidine and 4-aryl-1,2,3,6-tetrahydropyridine derivatives as corticotropin-releasing factor1 receptor antagonists. Bioorg Med Chem 2000, 8, 5, 1183.
【3】 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)	35384	bromo(3-fluorophenyl)magnesium		C₆H₄BrFMg	详情	详情
(III)	35385	tert-butyl 4-(3-fluorophenyl)-4-hydroxy-1-piperidinecarboxylate		C₁₆H₂₂FNO₃	详情	详情
(IV)	35386	4-(3-fluorophenyl)-1,2,3,6-tetrahydropyridine		C₁₁H₁₂FN	详情	详情
(V)	35387	2,4-dichloro-6-methylpyrimidine	5424-21-5	C₅H₄Cl₂N₂	详情	详情
(VI)	35388	2-chloro-4-[4-(3-fluorophenyl)-3,6-dihydro-1(2H)-pyridinyl]-6-methylpyrimidine		C₁₆H₁₅ClFN₃	详情	详情
(VII)	35389	4-isopropyl-2-(methylsulfanyl)phenylamine; 4-isopropyl-2-(methylsulfanyl)aniline		C₁₀H₁₅NS	详情	详情
(VIII)	35390	N-[4-[4-(3-fluorophenyl)-3,6-dihydro-1(2H)-pyridinyl]-6-methyl-2-pyrimidinyl]-N-[4-isopropyl-2-(methylsulfanyl)phenyl]amine; 4-[4-(3-fluorophenyl)-3,6-dihydro-1(2H)-pyridinyl]-N-[4-isopropyl-2-(methylsulfanyl)phenyl]-6-methyl-2-pyrimidinamine		C₂₆H₂₉FN₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

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.

参考文献中间体

合成目标

【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

Extended Information