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【结 构 式】

【分子编号】51623

【品名】(E,4R)-5-(3,4-dichlorophenyl)-4-(methylamino)-N-[(3R)-2-oxoazepanyl]-2-pentenamide

【CA登记号】

【 分 子 式 】C18H23Cl2N3O2

【 分 子 量 】384.30504

【元素组成】C 56.26% H 6.03% Cl 18.45% N 10.93% O 8.33%

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:(X)

(3,4-Dichlorophenyl)alanine methyl ester (I) was converted to the N-Boc amino ester (II), which was subsequently alkylated with iodomethane in the presence of Ag2O, yielding the N-methyl derivative (III). Partial reduction of the ester group of (III) to the aldehyde (IV) was carried out using DIBAL in toluene at -78 C. Horner-Emmons reaction of aldehyde (IV) with triethyl phosphonoacetate (V) furnished the arylpentenoate ester (VI), which was further hydrolyzed to acid (VII) with LiOH. Coupling of acid (VII) with D-3-amino-epsilon-caprolactam (VIII) gave rise to amide (IX). The N-Boc group of (IX) was removed by treatment with trifluoroacetic acid, and the resulting amine (X) was finally acylated with 3,5-bis(trifluoromethyl)benzoyl chloride to produce the target amide.

1 Gerspacher, M.; Von Sprecher, A.; Mah, R.; Roggo, S.; Stutz, S. (Novartis AG); Acylaminoalkenylene-amide derivs. as NK1 and NK2 antagonists. EP 0923550; JP 2001503387; US 6319917; WO 9807694 .
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) 51615 methyl (2R)-2-amino-3-(3,4-dichlorophenyl)propanoate C10H11Cl2NO2 详情 详情
(II) 51616 methyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-(3,4-dichlorophenyl)propanoate C15H19Cl2NO4 详情 详情
(III) 51617 methyl (2R)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-(3,4-dichlorophenyl)propanoate C16H21Cl2NO4 详情 详情
(IV) 51618 tert-butyl (1R)-1-(3,4-dichlorobenzyl)-2-oxoethyl(methyl)carbamate C15H19Cl2NO3 详情 详情
(V) 10019 Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate 867-13-0 C8H17O5P 详情 详情
(VI) 51619 ethyl (E,4R)-4-[(tert-butoxycarbonyl)(methyl)amino]-5-(3,4-dichlorophenyl)-2-pentenoate C19H25Cl2NO4 详情 详情
(VII) 51620 (E,4R)-4-[(tert-butoxycarbonyl)(methyl)amino]-5-(3,4-dichlorophenyl)-2-pentenoic acid C17H21Cl2NO4 详情 详情
(VIII) 51621 (3R)-3-amino-2-azepanone C6H12N2O 详情 详情
(IX) 51622 tert-butyl (1R,2E)-1-(3,4-dichlorobenzyl)-4-oxo-4-[[(3R)-2-oxoazepanyl]amino]-2-butenyl(methyl)carbamate C23H31Cl2N3O4 详情 详情
(X) 51623 (E,4R)-5-(3,4-dichlorophenyl)-4-(methylamino)-N-[(3R)-2-oxoazepanyl]-2-pentenamide C18H23Cl2N3O2 详情 详情
(XI) 18290 3,5-Bis(trifluoromethyl)benzoyl chloride 785-56-8 C9H3ClF6O 详情 详情
Extended Information