4-(3-chlorophenyl)-6-[(4-chlorophenyl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone -Drug Synthesis Database

【结构式】

【分子编号】46725

【品名】4-(3-chlorophenyl)-6-[(4-chlorophenyl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone

【CA登记号】

【分子式】C₂₇H₂₁Cl₂N₃O₂

【分子量】490.38816

【元素组成】C 66.13% H 4.32% Cl 14.46% N 8.57% O 6.53%

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：(VIII)

Cyclization of 3-(3-chlorophenyl)-N-phenyl-2-propenamide (I) by means of polyphosphoric acid (PPA) at 100 C gives 4-(3-chlorophenyl)-1,2,3,4-tetrahydroquinolin-2-one (II), which is condensed with 4-chlorobenzoic acid (III) by means of PPA at 140 C to yield 6-(4-chlorobenzoyl)-4-(3-chlorophenyl)-1,2,3,4-tetrahydroquinolin-2-one (IV). The dehydrogenation of (IV) by means of Br2 in bromobenzene at 160 C affords 6-(4-chlorobenzoyl)-4-(3-chlorophenyl)quinolin-2(1H)-one (V), which is methylated with iodomethane and NaOH/benzyltrimethylammonium chloride in THF to provide 6-(4-chlorobenzoyl)-4-(3-chlorophenyl)-1-methylquinolin-2(1H)-one (VI). Condensation of compound (VI) with 1-methylimidazole (VII) by means of butyllithium in THF gives the triaryl carbinol (VIII), which is finally treated with ammonia in THF to afford R-115777.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castaner, J.; Fernandez, R.; R-115777. Drugs Fut 2001, 26, 5, 453.
【2】 Venet, M.G.; Angibaud, P.R.; Muller, P.; Sanz, G.C. (Janssen Pharmaceutica NV); Farnesyl protein transferase inhibiting (imidazol-5-yl)methyl-2-quinolinone derivs.. EP 0865440; JP 1998511405; US 6037350; WO 9721701 .

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)	46720	(E)-3-(3-chlorophenyl)-N-phenyl-2-propenamide		C₁₅H₁₂ClNO	详情	详情
(II)	46721	4-(3-chlorophenyl)-3,4-dihydro-2(1H)-quinolinone		C₁₅H₁₂ClNO	详情	详情
(III)	18359	p-chlorobenzoic acid; 4-chlorobenzoic acid	74-11-3	C₇H₅ClO₂	详情	详情
(IV)	46722	6-(4-chlorobenzoyl)-4-(3-chlorophenyl)-3,4-dihydro-2(1H)-quinolinone		C₂₂H₁₅Cl₂NO₂	详情	详情
(V)	46723	6-(4-chlorobenzoyl)-4-(3-chlorophenyl)-2(1H)-quinolinone		C₂₂H₁₃Cl₂NO₂	详情	详情
(VI)	46724	6-(4-chlorobenzoyl)-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone		C₂₃H₁₅Cl₂NO₂	详情	详情
(VII)	38630	1-methyl-1H-imidazole	616-47-7	C₄H₆N₂	详情	详情
(VIII)	46725	4-(3-chlorophenyl)-6-[(4-chlorophenyl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone		C₂₇H₂₁Cl₂N₃O₂	详情	详情

Extended Information