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【结 构 式】 
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【药物名称】SSR-146977 【化学名称】N-[1-[3-[1-Benzoyl-3(R)-(3,4-dichlorophenyl)piperidin-3-yl]propyl]-4-phenylpiperidin-4-yl]-N',N'-dimethylurea 【CA登记号】264618-44-2, 264618-48-6 (benzoate), 264618-45-3 (fumarate), 264618-38-4 (hydrochloride), 264618-47-5 (succinate), 264618-49-7 ( 【 分 子 式 】C35H42Cl2N4O2 【 分 子 量 】621.65659 |
【开发单位】Sanofi-synthélabo (Originator) 【药理作用】Antiallergy/Antiasthmatic Drugs, Antidepressants, Antipsychotic Drugs, Asthma Therapy, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, RESPIRATORY DRUGS, Tachykinin NK3 Antagonists |
合成路线1
Acidic hydrolysis of 4-acetylamino-1-benzyl-4-phenylpiperidine (I) gives diamine (II). Subsequent acylation of (II) with dimethylcarbamoyl chloride affords urea (III). The N-benzyl protecting group is then removed by catalytic hydrogenolysis over Pd/C to furnish piperidine (IV)
| 【1】 Proietto, V.; Van Broeck, D.; Edmonds-Alt, X.; Aulombard, A. (Sanofi-Synthelabo); Ureidopiperidine derivs. as selective human NK3 receptor antagonists. EP 1119552; JP 2002527423; US 6465489; WO 0021931 . |
| 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) | 54993 | N-(1-benzyl-4-phenyl-4-piperidinyl)acetamide | C20H24N2O | 详情 | 详情 | |
| (II) | 54994 | 1-benzyl-4-phenyl-4-piperidinylamine; 1-benzyl-4-phenyl-4-piperidinamine | C18H22N2 | 详情 | 详情 | |
| (III) | 54995 | N'-(1-benzyl-4-phenyl-4-piperidinyl)-N,N-dimethylurea | C21H27N3O | 详情 | 详情 | |
| (IV) | 54996 | N,N-dimethyl-N'-(4-phenyl-4-piperidinyl)urea | C14H21N3O | 详情 | 详情 |
合成路线2
The previously reported (hydroxypropyl)piperidine derivative (V) is subjected to Swern oxidation to produce aldehyde (VI). Then, reductive amination of (VI) with piperidine (IV) in the presence of NaBH3CN affords the target compound
| 【1】 Proietto, V.; Van Broeck, D.; Edmonds-Alt, X.; Aulombard, A. (Sanofi-Synthelabo); Ureidopiperidine derivs. as selective human NK3 receptor antagonists. EP 1119552; JP 2002527423; US 6465489; WO 0021931 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 54996 | N,N-dimethyl-N'-(4-phenyl-4-piperidinyl)urea | C14H21N3O | 详情 | 详情 | |
| (V) | 29467 | [(3S)-3-(3,4-dichlorophenyl)-3-(3-hydroxypropyl)piperidinyl](phenyl)methanone | C21H23Cl2NO2 | 详情 | 详情 | |
| (VI) | 60037 | 3-[(3S)-1-benzoyl-3-(3,4-dichlorophenyl)piperidinyl]propanal | C21H21Cl2NO2 | 详情 | 详情 |