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【结 构 式】 
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【分子编号】55000 【品名】[(2R)-2-[2-(4-amino-4-phenyl-1-piperidinyl)ethyl]-2-(3,4-difluorophenyl)morpholinyl](phenyl)methanone 【CA登记号】 |
【 分 子 式 】C30H33F2N3O2 【 分 子 量 】505.6078464 【元素组成】C 71.27% H 6.58% F 7.52% N 8.31% O 6.33% |
合成路线1
该中间体在本合成路线中的序号：(XXIII)In an alternative process, the chiral morpholino alcohol (XIII) was activated as the sulfonate ester (XX) employing benzenesulfonyl chloride under phase-transfer conditions. Condensation of the alkyl sulfonate (XX) with 4-(tert-butoxycarbonylamino)-4-phenylpiperidine (XXI) afforded the N-substituted piperidine (XXII). The Boc protecting group of (XXII) was then removed by means of a methanolic solution of HCl, yielding the primary amine (XXIII). Alternatively, amine (XXIII) was synthesized by condensation of sulfonate (XX) with 4-amino-4-phenylpiperidine (XXIV) (obtained by catalytic hydrogenolysis of the N-benzyl piperidine (XVII)). Aminopiperidine (XXIII) was finally converted to the title urea by reaction with phosgene, followed by condensation with dimethylamine.
| 【1】 Bonnefoy, S.; Aulombard, A.; Lucas, E.; Bernon, F.; Burgos, A.; Cabos, C. (Sanofi-Synthélabo); Method for preparing (R)-(+)-3-[1-[2-(4-benzoyl-2-(2,3-difluorophenyl)morpholin-2-yl)ethyl]-4-phenylpiperidin-4-yl]-1,1-dimethylurea, its salts solvates and/or hydrates. FR 2787790; US 6392039; WO 0039126 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 54991 | [(2R)-2-(3,4-difluorophenyl)-2-(2-hydroxyethyl)morpholinyl](phenyl)methanone | C19H19F2NO3 | 详情 | 详情 | |
| (XVII) | 54994 | 1-benzyl-4-phenyl-4-piperidinylamine; 1-benzyl-4-phenyl-4-piperidinamine | C18H22N2 | 详情 | 详情 | |
| (XX) | 54997 | 2-[(2R)-4-benzoyl-2-(3,4-difluorophenyl)morpholinyl]ethyl benzenesulfonate | C25H23F2NO5S | 详情 | 详情 | |
| (XXI) | 54998 | tert-butyl 4-phenyl-4-piperidinylcarbamate | C16H24N2O2 | 详情 | 详情 | |
| (XXII) | 54999 | tert-butyl 1-{2-[(2R)-4-benzoyl-2-(3,4-difluorophenyl)morpholinyl]ethyl}-4-phenyl-4-piperidinylcarbamate | C35H41F2N3O4 | 详情 | 详情 | |
| (XXIII) | 55000 | [(2R)-2-[2-(4-amino-4-phenyl-1-piperidinyl)ethyl]-2-(3,4-difluorophenyl)morpholinyl](phenyl)methanone | C30H33F2N3O2 | 详情 | 详情 | |
| (XXIV) | 55001 | 4-phenyl-4-piperidinylamine; 4-phenyl-4-piperidinamine | C11H16N2 | 详情 | 详情 |