Diisopropylethylamine → Biphenyl-2-ylcarbamic Acid 1-[2-({3-[2-(3-{(S)-2-[(R)-2-(tert-Butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}phenyl)acetylamino]propyl}methylcarbamoyl)ethyl]piperidin-4-yl Ester

HRID 1097037Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1097037
[Si:1]([O:8][C@H:9]([C:25]1[CH:34]=[CH:33][C:32]([OH:35])=[C:31]2[C:26]=1[CH:27]=[CH:28][C:29](=[O:36])[NH:30]2)[CH2:10][NH:11][C@@H:12]([CH3:24])[CH2:13][C:14]1[CH:15]=[C:16]([CH2:20][C:21](O)=[O:22])[CH:17]=[CH:18][CH:19]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[O-]S(C(F)(F)F)(=O)=O.C(N(CC)C(C)C)(C)C.[NH2:54][CH2:55][CH2:56][CH2:57][N:58]([CH3:85])[C:59]([CH2:61][CH2:62][N:63]1[CH2:68][CH2:67][CH:66]([O:69][C:70](=[O:84])[NH:71][C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][C:73]=2[C:78]2[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=2)[CH2:65][CH2:64]1)=[O:60]>CN(C=O)C>[Si:1]([O:8][C@H:9]([C:25]1[CH:34]=[CH:33][C:32]([OH:35])=[C:31]2[C:26]=1[CH:27]=[CH:28][C:29](=[O:36])[NH:30]2)[CH2:10][NH:11][C@@H:12]([CH3:24])[CH2:13][C:14]1[CH:15]=[C:16]([CH2:20][C:21]([NH:54][CH2:55][CH2:56][CH2:57][N:58]([CH3:85])[C:59]([CH2:61][CH2:62][N:63]2[CH2:64][CH2:65][CH:66]([O:69][C:70](=[O:84])[NH:71][C:72]3[CH:77]=[CH:76][CH:75]=[CH:74][C:73]=3[C:78]3[CH:79]=[CH:80][CH:81]=[CH:82][CH:83]=3)[CH2:67][CH2:68]2)=[O:60])=[O:22])[CH:17]=[CH:18][CH:19]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2758875TrifluoromethanesulfonateHCID 66770193(3-{(S)-2-[(R)-2-(tert-butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}phenyl)acetic acidHCID 66770333Biphenyl-2-ylcarbamic acid 1-{2-[(3-aminopropyl)methylcarbamoyl]ethyl}piperidin-4-yl ester

Produkt 1

HCID 86646964Biphenyl-2-ylcarbamic Acid 1-[2-({3-[2-(3-{(S)-2-[(R)-2-(tert-Butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}phenyl)acetylamino]propyl}methylcarbamoyl)ethyl]piperidin-4-yl EsterAusbeute 24 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of (3-{(S)-2-[(R)-2-(tert-butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}phenyl)acetic acid (135 mg, 0.264 mmol); 2-chloropyridium triflate on Wang resin (polymer-supported Mukaiyama reagent) (1.19 mmol/g loading; 635 mg, 0.775 mmol) and N,N-diisopropylethylamine (132 μL, 0.755 mmol) in DMF (4.78 mL) was stirred at room temperature for 30 min. Biphenyl-2-ylcarbamic acid 1-{2-[(3-aminopropyl)methylcarbamoyl]ethyl}piperidin-4-yl ester (122 mg, 0.278 mmol) was added and this mixture was stirred at room temperature overnight. The mixture was filtered and the resin was washed with DCM (4 mL), MeOH (4 mL) and THF (4 mL). The filtrate was concentrated under reduced pressure and the residue was dissolved in DCM. This solution was washed with water (2×10 mL), saturated aqueous sodium bicarbonate (2×10 mL) and brine (1×10 mL); and then dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-20% MeOH in DCM) to give the title compound (59 mg, 24% yield) as a white solid.

Aufarbeitung

  1. filtrationThe mixture was filtered
  2. washthe resin was washed with DCM (4 mL), MeOH (4 mL) and THF (4 mL)
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. dissolutionthe residue was dissolved in DCM
  5. washThis solution was washed with water (2×10 mL), saturated aqueous sodium bicarbonate (2×10 mL) and brine (1×10 mL)
  6. dry with materialand then dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (0-20% MeOH in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-1346c8d0512447ad966175ccd3274b09
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08138345B2

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