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【结 构 式】

【分子编号】45637

【品名】(2R)-4-amino-2-chloro-4-oxobutyric acid

【CA登记号】

【 分 子 式 】C4H6ClNO3

【 分 子 量 】151.54928

【元素组成】C 31.7% H 3.99% Cl 23.39% N 9.24% O 31.67%

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:(II)

Diazotization of D-asparagine (I) in the presence of KCl afforded (R)-2-chlorosuccinamic acid (II) with retention of the configuration. Subsequent displacement of the chlorine atom of (II) with tert-butyl mercaptan provided thioether (III). Reduction of the carboxyl group of (III) by means of borane in THF gave alcohol (IV), which was converted to thioester (V) by esterification with thioacetic acid under Mitsunobu conditions. The chiral bromo acid (VII) (prepared by diazotization of L-leucine (VIII) in the presence of KBr) was then condensed with the thiol liberated from thioacetate (V) in the presence of NaOEt, yielding the corresponding thioether (VIII). Coupling of N-methyl-L-phenylalaninamide (IX) with carboxylic acid (VIII) using DCC and HOBt gave rise to amide (X). The S-tert-butyl group of (X) was then removed by means of 2-nitrobenzenesulfenyl chloride (XI) in HOAc, generating the disulfide (XII). Finally, the disulfide bond of (XII) was reductively cleaved with 2-mercaptoethanol to furnish the title thiol.

1 Schwartz, M.A.; Wart, H.V. (Florida State University); Mercaptosulfide metalloproteinase inhibitors. WO 9509833 .
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) 28237 R-(-)-Asparagine; S-(-)-2-Aminosuccinamic acid; D-asparagine 5794-13-8 C4H8N2O3 详情 详情
(II) 45637 (2R)-4-amino-2-chloro-4-oxobutyric acid C4H6ClNO3 详情 详情
(III) 45638 (2S)-4-amino-2-(tert-butylsulfanyl)-4-oxobutyric acid C8H15NO3S 详情 详情
(IV) 45639 (3S)-3-(tert-butylsulfanyl)-4-hydroxybutanamide C8H17NO2S 详情 详情
(V) 45640 S-[(2S)-4-amino-2-(tert-butylsulfanyl)-4-oxobutyl] ethanethioate C10H19NO2S2 详情 详情
(VI) 26057 L-Leucine 61-90-5 C6H13NO2 详情 详情
(VII) 16011 (2R)-2-bromo-4-methylpentanoic acid C6H11BrO2 详情 详情
(VIII) 45641 (2R)-2-[[(2S)-4-amino-2-(tert-butylsulfanyl)-4-oxobutyl]sulfanyl]-4-methylpentanoic acid C14H27NO3S2 详情 详情
(IX) 16015 (2S)-2-amino-N-methyl-3-phenylpropanamide C10H14N2O 详情 详情
(X) 45642 (2R)-2-[[(2S)-4-amino-2-(tert-butylsulfanyl)-4-oxobutyl]sulfanyl]-N-[(1S)-1-benzyl-2-(methylamino)-2-oxoethyl]-4-methylpentanamide C24H39N3O3S2 详情 详情
(XI) 45643 O-Nitrobenzenesulfenyl chloride; 2-nitrobenzenesulfenyl chloride; 2-nitrophenylsulfenyl chloride 7669-54-7 C6H4ClNO2S 详情 详情
(XII) 45644 (2R)-2-([(2S)-4-amino-2-[(2-nitrophenyl)disulfanyl]-4-oxobutyl]sulfanyl)-N-[(1S)-1-benzyl-2-(methylamino)-2-oxoethyl]-4-methylpentanamide C26H34N4O5S3 详情 详情
Extended Information