(2-[4-(4-fluorophenyl)-5-[2-(methylsulfanyl)-4-pyrimidinyl]-1H-imidazol-2-yl]-5-methyl-1,3-dioxan-5-yl)(4-morpholinyl)methanone -Drug Synthesis Database

【结构式】

【分子编号】49204

【品名】(2-[4-(4-fluorophenyl)-5-[2-(methylsulfanyl)-4-pyrimidinyl]-1H-imidazol-2-yl]-5-methyl-1,3-dioxan-5-yl)(4-morpholinyl)methanone

【CA登记号】

【分子式】C₂₄H₂₆FN₅O₄S

【分子量】499.5661432

【元素组成】C 57.7% H 5.25% F 3.8% N 14.02% O 12.81% S 6.42%

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：(XI)

Condensation of 2,2-bis(hydroxymethyl)propionic acid (VIII) with morpholine (IX) in the presence of DCC and HOBt gave amide (X). The cyclic ketal (XI) was then obtained by acid-catalyzed condensation of imidazole aldehyde (VII) with diol (X) using azeotropic removal of water. Oxidation of the sulfide group of (XI) with meta-chloroperbenzoic acid furnished sulfone (XII). The methylsulfonyl group of (XII) was finally displaced with cyclopropylamine (XIII) to provide the title compound

参考文献中间体

合成目标

【1】 Collis, A.J.; Wilsher, N.E.; Foster, M.L.; Redford, E.J.; McLay, I.M.; Page, K.M.; Maslen, C.; Halley, F.; Souness, J.E.; RPR203494 a pyrimidine analogue of the p38 inhibitor RPR200765A with an improved in vitro potency. Bioorg Med Chem Lett 2001, 11, 5, 693.
【2】 Halley, F.; Porter, B.; Bamborough, P.L.; Lewis, R.A.; Ratcliffe, A.J.; Wallace, P.A.; McLay, I.M.; McKenna, J.M.; Lythgoe, D.J.; Collis, A.J. (Rhone-Poulenc Rorer Ltd.); Imidazolyl-cyclic acetals. EP 0988301; WO 9856788 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	49201	4-(4-fluorophenyl)-5-[2-(methylsulfanyl)-4-pyrimidinyl]-1H-imidazole-2-carbaldehyde		C₁₅H₁₁FN₄OS	详情	详情
(VIII)	49202	3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid		C₅H₁₀O₄	详情	详情
(IX)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(X)	49203	3-hydroxy-2-(hydroxymethyl)-2-methyl-1-(4-morpholinyl)-1-propanone		C₉H₁₇NO₄	详情	详情
(XI)	49204	(2-[4-(4-fluorophenyl)-5-[2-(methylsulfanyl)-4-pyrimidinyl]-1H-imidazol-2-yl]-5-methyl-1,3-dioxan-5-yl)(4-morpholinyl)methanone		C₂₄H₂₆FN₅O₄S	详情	详情
(XII)	49205	(2-[4-(4-fluorophenyl)-5-[2-(methylsulfonyl)-4-pyrimidinyl]-1H-imidazol-2-yl]-5-methyl-1,3-dioxan-5-yl)(4-morpholinyl)methanone		C₂₄H₂₆FN₅O₆S	详情	详情
(XIII)	12263	Cyclopropylamine; Cyclopropanamine	765-30-0	C₃H₇N	详情	详情

Extended Information