Acetic Acid → tert-butyl(1-(4-(5-oxo-3-phenyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-2-yl)phenyl)cyclobutyl)carbamate

HRID 1509102Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1509102
[C:1]([O:5][C:6](=[O:31])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15](C(=O)C(C3C=CC=CC=3)=CN(C)C)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:32]1(=[O:40])[CH2:38][CH2:37][CH2:36][CH2:35][C:34](=O)[CH2:33]1.[C:41](O)(=O)[CH3:42]>>[C:1]([O:5][C:6](=[O:31])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:8]3[N:7]=[C:34]4[CH2:35][CH2:36][CH2:37][CH2:38][C:32](=[O:40])[C:33]4=[CH:10][C:9]=3[C:41]3[CH:42]=[CH:14][CH:13]=[CH:12][CH:17]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:3])([CH3:2])[CH3:4]

Komponenten

4

Edukt 3

HCID 176Acetic AcidHCID 4072367Cycloheptane-1,3-dioneHCID 66719111HCID 66719111, Verbindung

Produkt 1

HCID 123410895tert-butyl(1-(4-(5-oxo-3-phenyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-2-yl)phenyl)cyclobutyl)carbamateAusbeute 24 %

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of tert-butyl(1-(4-(3-(dimethylamino)-2-phenylacryloyl)phenyl)cyclobutyl)carbamate (119 mg, 0.28 mmol) in acetic acid (1 mL) was added molecular sieves (10 mg) and cycloheptane-1,3-dione (36 μL, 0.42 mmol) under nitrogen. The resulting mixture was heated at 100° C. for 2 h. After cooled down to room temperature, the mixture was partitioned between water (10 mL) and dichloromethane (10 mL). The layers were separated and the aqueous phase extracted into dichloromethane (2×10 mL). The combined organic phases were washed with saturated NaHCO3 solution (20 mL), brine (20 mL), dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 20% EtOAc in hexane) to give the title compound (32 mg, 24%). 1H NMR (500 MHz, CDCl3): 8.09 (1H, s), 7.38 (2H, d), 7.30 (2H,d), 7.25-7.24 (3H, m), 7.19-7.17 (2H, m), 5.04 (1H, br s), 3.29 (2H,t), 2.87 (2H, t), 2.60-2.25 (4H, m), 2.07-2.01 (3H, m), 1.99-1.94 (2H, m), 1.84-1.75 (1H, m), 1.42-1.15 (9H, br).

Aufarbeitung

  1. temperatureAfter cooled down to room temperature
  2. customthe mixture was partitioned between water (10 mL) and dichloromethane (10 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase extracted into dichloromethane (2×10 mL)
  5. washThe combined organic phases were washed with saturated NaHCO3 solution (20 mL), brine (20 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure
  9. customThe resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 20% EtOAc in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-a9437956fde346fa9bd6cb7e6b5b5941
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09221838B2

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