Ethanol → (2S,4R)-3-[3-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-propyl]-5-methyl-3H-imidazole-4-carboxylic acid

HRID 1786043노트

반응식

HRID 1786043 반응식
C([O:3][C:4]([C:6]1[N:7]([CH2:12][CH2:13][CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([N:24]3[C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[C@H:27]([N:34]([C:42](=[O:44])[CH3:43])[C:35]4[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=4)[CH2:26][C@@H:25]3[CH3:45])=[O:23])=[CH:18][CH:17]=2)[CH:8]=[N:9][C:10]=1[CH3:11])=[O:5])C.C(O)C.[OH-].[Na+]>O1CCCC1>[C:42]([N:34]([C:35]1[CH:36]=[CH:37][C:38]([Cl:41])=[CH:39][CH:40]=1)[C@H:27]1[C:28]2[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:24]([C:22]([C:19]2[CH:20]=[CH:21][C:16]([O:15][CH2:14][CH2:13][CH2:12][N:7]3[C:6]([C:4]([OH:5])=[O:3])=[C:10]([CH3:11])[N:9]=[CH:8]3)=[CH:17][CH:18]=2)=[O:23])[C@@H:25]([CH3:45])[CH2:26]1)(=[O:44])[CH3:43]

참가 물질

5

반응물 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 68918710(2S,4R)-3-[3-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-propyl]-5-methyl-3H-imidazole-4-carboxylic acid ethyl ester

생성물 1

HCID 57595510(2S,4R)-3-[3-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-propyl]-5-methyl-3H-imidazole-4-carboxylic acid수율 61%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide was dissolved in DMF at room temperature and K2CO3 was added. 3-(3-Bromo-propyl)-5-methyl-3H-imidazole-4-carboxylic acid ethyl ester (prepared from the dibromide and the corresponding imidazole with NaH in THF) was added and the reaction was allowed to heat to 80° C. overnight. The reaction mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and water, then extracted three times with ethyl acetate, dried over MgSO4, filtered and concentrated down. The crude residue was purified by silica gel chromatography (2% MeOH/95% CH2Cl2 to 10% MeOH/90% CH2Cl2) to afford (2S,4R)-3-[3-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-propyl]-5-methyl-3H-imidazole-4-carboxylic acid ethyl ester. The ester (0.080 g, 0.12 mmol) was hydrolyzed to the acid by dissolving in tetrahydrofuran and ethanol and sodium hydroxide (1N) was added. The mixture was stirred at room temperature 16 hours. The mixture was cooled to room temperature, acidified to form a white precipitate. The solid was filtered to give (2S,4R)-3-[3-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-propyl]-5-methyl-3H-imidazole-4-carboxylic acid in 61% yield.

후처리

  1. temperatureThe mixture was cooled to room temperature
  2. customto form a white precipitate
  3. filtrationThe solid was filtered

출처 및 근거

ORD 기록
ord-df515fa8651a471380cf6635929a49d5
출처 데이터셋
uspto-grants-2009_03
특허 번호
US07504508B2

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