Trifluoroacetic acid → HCID 86732032, Verbindung

HRID 527421Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 527421
[CH3:1][S:2][C:3]1[N:4]=[CH:5][C:6]2[CH:12]=[CH:11][C:10](=[O:13])[N:9]([C:14]3[CH:15]=[C:16]([NH:20][C:21](=O)[O:22]C(C)(C)C)[CH:17]=[CH:18][CH:19]=3)[C:7]=2[N:8]=1.[C:28](O)([C:30](F)(F)F)=O.C(Cl)(=O)C=C>C(Cl)Cl>[CH3:1][S:2][C:3]1[N:4]=[CH:5][C:6]2[CH:12]=[CH:11][C:10](=[O:13])[N:9]([C:14]3[CH:15]=[C:16]([NH:20][C:21](=[O:22])[CH:28]=[CH2:30])[CH:17]=[CH:18][CH:19]=3)[C:7]=2[N:8]=1

Komponenten

5

Edukt 3

HCID 6422Trifluoroacetic acidHCID 13140Acryloyl chloride2×HCID 86732006tert-butyl (3-(2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate

Produkt 1

HCID 86732032HCID 86732032, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a suspension of tert-butyl (3-(2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate (51) (651 mg, 1.69 mmol) in 10 mL of DCM at RT was added 3 mL of TFA. The resulting homogeneous solution was stirred at RT for 1 h. It was concentrated under reduced pressure. The residue was in dissolved in 20 mL of DCM and cooled with an ice bath, then treated with DEIA (1.47 mL, 8.47 mmol) followed by acryloyl chloride (0.16 mL, 2.03 mmol). After 20 min at 0° C., additional acryloyl chloride (80 μL) was added in. The resulting mixture was stirred for 5 min, then quenched with 0.5 N NaOH (10 mL). The layers were separated and the water layer was extracted with 50 mL of DCM. The combined DCM extracts were washed with 2×5 mL of brine, dried over Na2SO4 and concentrated. The residue was stirred in 25 mL of EtOAc. The insoluble solid was filtered and dried to give 310 mg of N-(3-(2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide (11a). The filtrate was concentrated and purified on a silica gel column (35-100% EtOAc in hexanes) to give 140 mg of N-(3-(2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide (11a). m/z (ESI, +ve ion) 338.9 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.40 (1H, s), 8.95 (1H, s), 8.05 (1H, d, J=9.6 Hz), 7.68 (2H, m), 7.49 (1H, t, J=7.8 Hz), 7.04 (1H, d, J=8.2 Hz), 6.72 (1H, d, J=9.6 Hz), 6.46 (1H, dd, J=17.0, 10.2 Hz), 6.26 (1H, d, J=16.8 Hz), 5.78 (1H, d, J=9.6 Hz), 2.20 (3H, s).

Aufarbeitung

  1. concentrationIt was concentrated under reduced pressure
  2. dissolutionin dissolved in 20 mL of DCM
  3. temperaturecooled with an ice bath
  4. additiontreated with DEIA (1.47 mL, 8.47 mmol)
  5. waitAfter 20 min at 0° C.
  6. stirringThe resulting mixture was stirred for 5 min
  7. customquenched with 0.5 N NaOH (10 mL)
  8. customThe layers were separated
  9. extractionthe water layer was extracted with 50 mL of DCM
  10. washThe combined DCM extracts were washed with 2×5 mL of brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. stirringThe residue was stirred in 25 mL of EtOAc
  14. filtrationThe insoluble solid was filtered
  15. customdried

Quellen und Nachweise

ORD-Eintrag
ord-d73e54105f5c477facf6c22c23c5f557
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346801B2

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