Trifluoroacetic acid → (2S,3S)-3-methyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]pentanoic acid trifluoroacetat

HRID 1174122Notes

Reaction equation

HRID 1174122 reaction equation
[NH2:1][CH2:2][CH2:3][NH:4][C@@H:5]([C@@H:13]([CH3:16])[CH2:14][CH3:15])[C:6]([O:8]C(C)(C)C)=[O:7].[N:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]([CH:27]=O)=[CH:19][CH:18]=1.[BH4-].[Na+].[C:31](=O)(OC1C=CC([N+]([O-])=O)=CC=1)[O:32]C1C=CC([N+]([O-])=O)=CC=1.[F:53][C:54]([F:59])([F:58])[C:55]([OH:57])=[O:56]>C1C=CC=CC=1.C(O)C.ClCCCl.ClCCl>[F:53][C:54]([F:59])([F:58])[C:55]([OH:57])=[O:56].[CH3:16][C@@H:13]([CH2:14][CH3:15])[C@H:5]([N:4]1[CH2:3][CH2:2][N:1]([CH2:27][C:20]2[C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:17]=[CH:18][CH:19]=2)[C:31]1=[O:32])[C:6]([OH:8])=[O:7]

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 780724-QuinolinecarboxaldehydeHCID 78756Bis(4-nitrophenyl) carbonateHCID 4311764Sodium borohydrideHCID 86598803tert-butyl(2S,3S)-2-[(2-aminoethyl)amino]-3-methylpentanoate

Product 1

HCID 67408554(2S,3S)-3-methyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]pentanoic acid trifluoroacetatYield 48%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 241BenzeneSolventHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

A solution containing the product from Example 3G (2.0 g, 8.69 mmol) in a mixture of benzene (40 mL) and ethanol (40 mL) was treated with 4-quinolinecarboxaldehyde (1.4 g, 8.91 mmol), heated at 70° C. for 2 hours, cooled to 25° C., treated with sodium borohydride (1.0 g, 26.75 mmol), stirred at 25° C. for 16 hours, quenched with sodium bicarbonate solution and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated. A solution of the residue (8.69 mmol) in 1,2-dichloroethane (300 mL) was treated with bis(4-nitrophenyl) carbonate (3.0 g, 9.86 mmol), heated at 70° C. for 16 hours, and partitioned between ethyl acetate and saturated NaHCO3. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated. A solution of the residue (8.69 mmol) in dichloromethane (40 mL) was treated with trifluoracetic acid (40 mL), stirred at 25° C. for 1 hour and concentrated. The residue was chromatographed on silica gel eluting with 0-5% methanol in dichloromethane. A second purification using reversed phase chromatography on a C18 column, eluting with 5-100% acetonitrile in water (0.1% TFA) afforded the title compound (1.91 g, 48% yield).

Workup

  1. temperaturecooled to 25° C.
  2. customquenched with sodium bicarbonate solution
  3. custompartitioned between ethyl acetate and water
  4. washThe organic phase was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. temperatureheated at 70° C. for 16 hours
  9. custompartitioned between ethyl acetate and saturated NaHCO3
  10. washThe organic phase was washed with brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. stirringstirred at 25° C. for 1 hour
  15. concentrationconcentrated
  16. customThe residue was chromatographed on silica gel eluting with 0-5% methanol in dichloromethane
  17. customA second purification
  18. washeluting with 5-100% acetonitrile in water (0.1% TFA)

Sources & evidence

ORD record
ord-b97e7df17db14db29d27016780dbb5cc
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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