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【结 构 式】

【分子编号】63989

【品名】N-methoxy-2-[methoxy(methyl)amino]-N-methyl-2-oxoacetamide

【CA登记号】

【 分 子 式 】C6H12N2O4

【 分 子 量 】176.17236

【元素组成】C 40.91% H 6.87% N 15.9% O 36.33%

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:(XII)

Condensation of oxalyl chloride (XI) with N,O-dimethylhydroxylamine produces N,N'-dimethyl-N,N'-dimethoxy oxamide (XII). This is then condensed with cyclobutylmethylmagnesium bromide (XIII) to afford the ketoamide (XIV). Asymmetric keto group reduction employing (R)-alpine borane leads to the (S)-alcohol (XV) in 91% enantiomeric excess. Hydrolysis of the N-methoxyamide function of (XV) to provide hydroxyacid (XVI) is then accomplished employing potassium tert-butoxide in the presence of the equimolecular amount of H2O in THF. Alkylation of hydroxyacid (XVI) with benzyl bromide and Et3N furnishes the corresponding benzyl ester (XVII). Treatment of (XVII) with trifluoromethanesulfonic anhydride gives rise to triflate (XVIII), which is further condensed with pyrrolidine (X) to produce (XIX). After desilylation of (XIX) with tetrabutylammonium fluoride, the resultant alcohol (XX) is oxidized to aldehyde (XXI) under Swern conditions.

1 Mills, S.G.; Kim, D.; Hale, J.; MacCoss, M.; Berk, S.; Chapman, K.; Lynch, C.; Caldwell, C.; Willoughby, C.; Kim, R.M. (Merck & Co., Inc.); Pyrrolidine modulators of chemokine receptor activity. US 6498161; WO 0059498 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(X) 63988 (3R,4S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(3-fluorophenyl)pyrrolidine; tert-butyl(dimethyl)silyl [(3R,4S)-4-(3-fluorophenyl)pyrrolidinyl]methyl ether C17H28FNOSi 详情 详情
(XI) 29841 Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride 79-37-8 C2Cl2O2 详情 详情
(XII) 63989 N-methoxy-2-[methoxy(methyl)amino]-N-methyl-2-oxoacetamide C6H12N2O4 详情 详情
(XIII) 63990 bromo(cyclobutylmethyl)magnesium C5H9BrMg 详情 详情
(XIV) 63991 3-cyclobutyl-N-methoxy-N-methyl-2-oxopropanamide C9H15NO3 详情 详情
(XV) 63992 (2S)-3-cyclobutyl-2-hydroxy-N-methoxy-N-methylpropanamide C9H17NO3 详情 详情
(XVI) 63993 (2S)-3-cyclobutyl-2-hydroxypropanoic acid C7H12O3 详情 详情
(XVII) 63994 benzyl (2S)-3-cyclobutyl-2-hydroxypropanoate C14H18O3 详情 详情
(XVIII) 63995 benzyl (2S)-3-cyclobutyl-2-{[(trifluoromethyl)sulfonyl]oxy}propanoate C15H17F3O5S 详情 详情
(XIX) 63997 benzyl (2R)-2-[(3R,4S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(3-fluorophenyl)pyrrolidinyl]-3-cyclobutylpropanoate C31H44FNO3Si 详情 详情
(XX) 63996 benzyl (2R)-3-cyclobutyl-2-[(3S,4R)-3-(3-fluorophenyl)-4-(hydroxymethyl)pyrrolidinyl]propanoate C25H30FNO3 详情 详情
(XXI) 63998 benzyl (2R)-3-cyclobutyl-2-[(3S,4R)-3-(3-fluorophenyl)-4-formylpyrrolidinyl]propanoate C25H28FNO3 详情 详情
Extended Information