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

HRID 1174122
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HRID 1174122 반응식
[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]
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참가 물질

10

반응물 5

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

생성물 1

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

시약·촉매·용매 4

HCID 111,2-Dichloroethane용매HCID 241Benzene용매HCID 702Ethanol용매HCID 6344Dichloromethane용매

반응 조건

온도
70 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-b97e7df17db14db29d27016780dbb5cc
출처 데이터셋
uspto-grants-2010_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07834043B2

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