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【结 构 式】

【分子编号】43981

【品名】allyl (2R,4R)-2-(4-[[[(allyloxy)carbonyl](methyl)amino]methyl]phenyl)-4-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-1-pyrrolidinecarboxylate

【CA登记号】

【 分 子 式 】C23H32N2O5S

【 分 子 量 】448.58356

【元素组成】C 61.58% H 7.19% N 6.24% O 17.83% S 7.15%

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:(IX)

The Grignard condensation of the chiral pyrrolidinone (I) with 4-(dimethoxymethyl)phenylmagnesium bromide (II) in THF, followed by reduction with NaBH4, gives the aminoalcohol (III), which is cyclized to the pyrrolidine (IV) by means of MsCl and TEA in dichloromethane. Hydrolysis of the dimethyl acetal of (IV), followed by separation of the resulting diastereomeric mixture of aldehydes, yields the desired diastereomer (V). The reduction of (V) with NaBH4, followed by reaction with Ms-Cl in dichloromethane, affords the mesylate (VI), which by reaction with methylamine provides the secondary amine (VII). The protection of (VII) with allyl chloroformate and TEA, cleavage of the silyl-protecting group gives the hydroxy pyrrolidine (VIII), which is treated with MsCl and TEA to yield the mesylate (IX). The reaction of (IX) with potassium thioacetate in hot DMF affords the sulfanyl pyrrolidine (X), which is condensed with the penem diphenyl phosphate (XI) by means of DIEA in acetonitrile to provide the protected intermediate (XII). Finally, (XII) is converted into the target compound by reaction with PdCl2(PPh3)2 and Bu3SnH in dichloromethane/water.

1 Imamura, H.; et al.; A novel 1beta-methylcarbapenem, J-111,225: Effects of the C-3 and C-5 stereochemistry of the pyrrolidinylthio side chain on antibacterial activities. J Antibiot 2000, 53, 3, 314.
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) 30852 tert-butyl (2R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-(4-formylphenyl)-1-pyrrolidinecarboxylate C22H35NO4Si 详情 详情
(II) 30851 bromo[4-(dimethoxymethyl)phenyl]magnesium C9H11BrMgO2 详情 详情
(III) 43977 tert-butyl (2R)-2-[[tert-butyl(dimethyl)silyl]oxy]-4-[4-(dimethoxymethyl)phenyl]-4-hydroxybutylcarbamate C24H43NO6Si 详情 详情
(IV) 43978 tert-butyl (4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-[4-(dimethoxymethyl)phenyl]-1-pyrrolidinecarboxylate C24H41NO5Si 详情 详情
(V) 30852 tert-butyl (2R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-(4-formylphenyl)-1-pyrrolidinecarboxylate C22H35NO4Si 详情 详情
(VI) 30871 tert-butyl (2R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-[4-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)phenyl]-1-pyrrolidinecarboxylate C25H43NO4SSi 详情 详情
(VII) 43979 tert-butyl (2R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-[4-[(methylamino)methyl]phenyl]-1-pyrrolidinecarboxylate C23H40N2O3Si 详情 详情
(VIII) 43980 allyl (2R,4R)-2-(4-[[[(allyloxy)carbonyl](methyl)amino]methyl]phenyl)-4-hydroxy-1-pyrrolidinecarboxylate C20H26N2O5 详情 详情
(IX) 43981 allyl (2R,4R)-2-(4-[[[(allyloxy)carbonyl](methyl)amino]methyl]phenyl)-4-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-1-pyrrolidinecarboxylate C23H32N2O5S 详情 详情
(X) 43982 allyl (2R,4S)-2-(4-[[[(allyloxy)carbonyl](methyl)amino]methyl]phenyl)-4-sulfanyl-1-pyrrolidinecarboxylate C20H26N2O4S 详情 详情
(XI) 32617 allyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate C25H26NO8P 详情 详情
(XII) 43983 allyl (4R,5S,6S)-3-[[(3S,5R)-1-[(allyloxy)carbonyl]-5-(4-[[[(allyloxy)carbonyl](methyl)amino]methyl]phenyl)pyrrolidinyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate C33H41N3O8S 详情 详情
Extended Information