Acetic Acid → 4'-{2-Ethoxy-4-ethyl-5-[((S)-2-mercapto-4-methylpentanoylamino)methyl]imidazol-1-ylmethyl}-3'-fluorobiphenyl-2-carboxylic Acid

HRID 45915Notes

Reaction equation

HRID 45915 reaction equation
C([S:4][C@@H:5]([CH2:37][CH:38]([CH3:40])[CH3:39])[C:6]([NH:8][CH2:9][C:10]1[N:14]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[C:23]([C:28]([OH:30])=[O:29])=[CH:24][CH:25]=[CH:26][CH:27]=3)=[CH:18][C:17]=2[F:31])[C:13]([O:32][CH2:33][CH3:34])=[N:12][C:11]=1[CH2:35][CH3:36])=[O:7])(=O)C.C(S)[C@@H](O)[C@H](O)CS.CC(O)=O.O>CO>[CH2:33]([O:32][C:13]1[N:14]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[C:23]([C:28]([OH:30])=[O:29])=[CH:24][CH:25]=[CH:26][CH:27]=3)=[CH:18][C:17]=2[F:31])[C:10]([CH2:9][NH:8][C:6](=[O:7])[C@@H:5]([SH:4])[CH2:37][CH:38]([CH3:39])[CH3:40])=[C:11]([CH2:35][CH3:36])[N:12]=1)[CH3:34]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 446094D-1,4-DithiothreitolHCID 510415714'-{5-[((S)-2-Acetylsulfanyl-4-methylpentanoylamino)methyl]-2-ethoxy-4-ethylimidazol-1-ylmethyl}-3'-fluorobiphenyl-2-carboxylic Acid

Product 1

HCID 451026014'-{2-Ethoxy-4-ethyl-5-[((S)-2-mercapto-4-methylpentanoylamino)methyl]imidazol-1-ylmethyl}-3'-fluorobiphenyl-2-carboxylic AcidYield 56.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Crystalline 4′-{5-[((S)-2-acetylsulfanyl-4-methylpentanoylamino)methyl]-2-ethoxy-4-ethylimidazol-1-ylmethyl}-3′-fluorobiphenyl-2-carboxylic acid (2.3 g, 4 mmol, 1 eq.) and DTT (62 mg, 0.4 mmol, 0.1 eq.) was dissolved in MeOH (30 mL). The resulting solution was degassed with nitrogen (3 times) and cooled at 0° C. NaOMe (25% in MeOH, 1.7 mL) was added and the mixture was stirred at 0° C. for 30 minutes. AcOH (3 g, 50 mmol, 4 eq.) was added to quench the reaction at 0° C. The mixture was warmed to 20° C. Deionized water (10 mL) was added slowly. The mixture was stirred at 20° C. for 3 hours and then stirred at 4° C. for 1 hour until precipitates were formed. The solids were filtered and washed with MeOH/H2O (2:1; 30 mL), then dried under nitrogen at 20° C. for 48 hours to yield the title crystalline compound (1.2 g).

Workup

  1. customThe resulting solution was degassed with nitrogen (3 times)
  2. additionNaOMe (25% in MeOH, 1.7 mL) was added
  3. customto quench
  4. customthe reaction at 0° C
  5. temperatureThe mixture was warmed to 20° C
  6. stirringThe mixture was stirred at 20° C. for 3 hours
  7. stirringstirred at 4° C. for 1 hour
  8. customuntil precipitates
  9. customwere formed
  10. filtrationThe solids were filtered
  11. washwashed with MeOH/H2O (2:1; 30 mL)
  12. customdried under nitrogen at 20° C. for 48 hours

Sources & evidence

ORD record
ord-0c5cfed674144a6abd06c55ec52720d8
Source dataset
uspto-grants-2013_09
Patent number
US08541597B2

Reaction notes

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