1,2-Dichloroethane → 4'-{5-[((S)-2-acetylsulfanyl-4-methylpentanoylamino)methyl]-2-ethoxy-4-ethylimidazol-1-ylmethyl}-3'-fluorobiphenyl-2-carboxylic acid t-butyl ester

HRID 2264677Notes

Reaction equation

HRID 2264677 reaction equation
[C:1]([O:5][C:6]([C:8]1[C:9]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][N:21]3[C:25]([CH2:26][NH2:27])=[C:24]([CH2:28][CH3:29])[N:23]=[C:22]3[O:30][CH2:31][CH3:32])=[C:16]([F:33])[CH:15]=2)=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:34]([S:37][C@@H:38]([CH2:42][CH:43]([CH3:45])[CH3:44])[C:39](O)=[O:40])(=[O:36])[CH3:35].CN1CCOCC1.ON1C2N=CC=CC=2N=N1.CN(C=O)C.C(Cl)CCl>>[C:1]([O:5][C:6]([C:8]1[C:9]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][N:21]3[C:25]([CH2:26][NH:27][C:39](=[O:40])[C@@H:38]([S:37][C:34](=[O:36])[CH3:35])[CH2:42][CH:43]([CH3:45])[CH3:44])=[C:24]([CH2:28][CH3:29])[N:23]=[C:22]3[O:30][CH2:31][CH3:32])=[C:16]([F:33])[CH:15]=2)=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 6

HCID 111,2-DichloroethaneHCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 181649HOAtHCID 14505484(S)-2-(Acetylthio)-4-methylpentanoic acidHCID 510413374'-(5-Aminomethyl-2-ethoxy-4-ethylimidazol-1-ylmethyl)-3'-fluorobiphenyl-2-carboxylic acid t-butyl ester

Product 1

HCID 251141774'-{5-[((S)-2-acetylsulfanyl-4-methylpentanoylamino)methyl]-2-ethoxy-4-ethylimidazol-1-ylmethyl}-3'-fluorobiphenyl-2-carboxylic acid t-butyl ester

Conditions

Temperature
0 °C

Procedure

4′-(5-Aminomethyl-2-ethoxy-4-ethylimidazol-1-ylmethyl)-3′-fluorobiphenyl-2-carboxylic acid t-butyl ester (5.0 g, 11.0 mmol), (S)-2-acetylsulfanyl-4-methylpentanoic acid (dicyclohexylamine salt; 2.1 g, 11.0 mmol), 4-methylmorpholine (1.2 mL, 11.0 mmol), and 1-hydroxy-7-azabenzotriazole (1.5 g, 11.0 mmol) were combined and dissolved in DMF (120 mL, 1.6 mol) and then cooled at 0° C. for 10 minutes. EDC (2 mL, 11.0 mmol) was added and the mixture was stirred at 0° C. for 1 hour and then at room temperature for 2 hours. The reaction was quenched with water (100 mL), the product extracted with EtOAc (100 mL), and then concentrated. The mixture was purified by column chromatography (0-50% EtOAc:hexanes) to obtain the acetylsulfanyl ester intermediate, 4′-{5-[((S)-2-acetylsulfanyl-4-methylpentanoylamino)methyl]-2-ethoxy-4-ethylimidazol-1-ylmethyl}-3′-fluorobiphenyl-2-carboxylic acid t-butyl ester.

Workup

  1. waitat room temperature for 2 hours
  2. customThe reaction was quenched with water (100 mL)
  3. extractionthe product extracted with EtOAc (100 mL)
  4. concentrationconcentrated
  5. customThe mixture was purified by column chromatography (0-50% EtOAc:hexanes)

Sources & evidence

ORD record
ord-543bed61f33d437d99f40548e35387eb
Source dataset
uspto-grants-2010_12
Patent number
US07855221B2

Reaction notes

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