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 1786043Notes

Reaction equation

HRID 1786043 reaction equation
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]

Participants

5

Reactant 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

Product 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 acidYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(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.

Workup

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

Sources & evidence

ORD record
ord-df515fa8651a471380cf6635929a49d5
Source dataset
uspto-grants-2009_03
Patent number
US07504508B2

Reaction notes

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