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【结 构 式】

【分子编号】65797

【品名】3-(Dimethylamino)-1-(naphthalen-1-yl)propan-1-one; (2-alpha-Naphthoylethyl)dimethylamine; 2-(Dimethylamino)ethyl 1-naphthyl ketone

【CA登记号】10320-49-7

【 分 子 式 】C15H17NO

【 分 子 量 】227.30612

【元素组成】C 79.26% H 7.54% N 6.16% O 7.04%

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:(VI)

Condensation of 4-bromoaniline (I) with 3-phenylpropionyl chloride (II) by means of triethylamine in dichloromethane gives the propionamide (III), which is cyclized with dimethylformamide by means of POCl3 in hot DMF to yield 3-benzyl-6-bromo-2-chloroquinoline (IV). Reaction of compound (IV) with NaOMe in refluxing methanol affords the 2-methoxyquinoline derivative (V), which is condensed with 3-(dimethylamino)-1-(1-naphthyl)propanone (VI) by means of BuLi in THF to provide a mixture of two diastereomeric racemates (R*,R*/R*,S*) (VII) that are separated by column chromatography. Finally, the desired (R*,S*)-racemic mixture is submitted to chiral chromatography (1). Scheme 1.
In an improved process, 3-benzyl-6-bromo-2-methoxyquinoline (V) is condensed with 3-(dimethylamino)-1-(1-naphthyl)propanone (VI) by means of LDA in THF and then treated with AcOH to afford the tertiary alcohol (VII). Finally, alcohol (VII) is submitted to optical resolution by crystallization with chiral 4-hydroxydinaphtho[2,1-d:1’,2’-f][1,3,2]dioxaphosphepin 4-oxide (2). Scheme 1.

1 Van Gestel, J.F.E., Venet, M.G., Vernier, D.F.J., Decrane, L.F.B., Poignet, H.J.J. (Janssen Pharmaceutica NV). Quinoline derivatives and their use as mycobacterial inhibitors. CA 2493225, EP 1527050, JP 2006504658, WO 2004011436.
2 Porstmann, F.R., Horns, S., Bader, T. (Janssen Pharmaceutica NV). Process for preparing (alphaS,betaR)-6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-1-naphthalenyl-beta-phenyl-3-quinolineethanol. CA 2606675, EP 1888604, US 2008200683, WO 2006125769.
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) 22531 4-Bromoaniline; 4-Bromophenylamine 106-40-1 C6H6BrN 详情 详情
(II) 16240 3-phenylpropanoyl chloride; Hydrocinnamoylchloride 645-45-4 C9H9ClO 详情 详情
(III) 65794 N-(4-Bromophenyl)-3-Phenylpropanamide 316146-27-7 C15H14BrNO 详情 详情
(IV) 65795 6-Bromo-2-chloro-3-(phenylmethyl)quinoline 654655-68-2 C16H11BrClN 详情 详情
(V) 65796 3-Benzyl-6-bromo-2-methoxyquinoline 654655-69-3 C17H14BrNO 详情 详情
(VI) 65797 3-(Dimethylamino)-1-(naphthalen-1-yl)propan-1-one; (2-alpha-Naphthoylethyl)dimethylamine; 2-(Dimethylamino)ethyl 1-naphthyl ketone 10320-49-7 C15H17NO 详情 详情
(VII) 65798 6-Bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-1-naphthalenyl-beta-phenyl-3-quinolineethanol 654655-80-8 C32H31BrN2O2 详情 详情
Extended Information