Trifluoroacetic acid → HCID 178493878, Verbindung

HRID 339769Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 339769
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:7]([CH2:23][CH2:24][N:25]=3)[C:8]([NH:14][C:15]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[O:16])=[N:9][C:10]=2[C:11]=1[O:12][CH3:13].C(O)(C(F)(F)F)=O.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:44][C@@H:45]1[O:47][CH2:46]1)(=O)=O>CN(C=O)C>[CH3:13][O:12][C:11]1[C:10]2[N:9]=[C:8]([NH:14][C:15](=[O:16])[C:17]3[CH:22]=[CH:21][CH:20]=[N:19][CH:18]=3)[N:7]3[CH2:23][CH2:24][N:25]=[C:6]3[C:5]=2[CH:4]=[CH:3][C:2]=1[O:1][CH2:44][C@H:45]1[CH2:46][O:47]1

Komponenten

6

Edukt 4

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 12461091(R)-glycidyl methanesulfonate2×HCID 178493831HCID 178493831, Verbindung2×

Produkt 1

HCID 178493878HCID 178493878, VerbindungAusbeute 69,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of N-{8-hydroxy-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl}pyridine-3-carboxamide (Intermediate I, Step 2 (used as bis-TFA salt), 1.50 g, 2.65 mmol) and caesium carbonate (4.32 g, 13.3 mmol, 5.0 equiv.) in DMF (37 mL) was stirred at room temperature for 1 h, then was treated with (R)-glycidyl methanesulfonate (Intermediate F, Step 1, 21.2 mL, 0.25 M in DMF, 5.31 mmol, 2.0 equiv.). The resulting mixture was stirred at room temperature for 16 h at 60° C., then was cooled to room temperature and concentrated under reduced pressure. The resulting residue was seperated between water (50 mL) and a 4:1 CH2Cl2/isopropanol solution (50 mL). The organic phase was washed with a concentrated sodium bicarbonate solution, dried (anh. sodium sulfate), and concentrated under reduced pressure. The resulting material was triturated with EtOH and dried under reduced pressure to give N-{7-methoxy-8-[(2R)-oxiran-2-ylmethoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl}nicotinamide (0.72 g, 69%): HPLC ret. time 0.94 min.; 1H NMR (DMSO-d6+1 drop TFA-d) δ 2.75 (dd, J=2.5, 5.1 Hz, 1H), 2.88 (app t, J=4.7, 1H), 3-42-3.47 (m, 1H), 4.01 (s, 3H), 4.14 (dd, J=6.6, 11.6 Hz, 1H), 4.20-4.29 (m, 3H), 4.52-4.59 (m, 2H), 4.68 (dd, J=2.3, 11.6 Hz, 1H), 7.47 (d, J=9.4 Hz, 1H), 7.92 (dd, J=5.6, 7.8 Hz, 1H), 8.03 (d, J=9.1 Hz, 1H), 8.90 (br d, J=7.8 Hz, 1H), 8.97 (dd, J=1.5, 5.6 Hz, 1H), 9.49 (d, J=1.5 Hz, 1H); mass spectrum m/z 394 ((M+1)+, 11%).

Aufarbeitung

  1. stirringThe resulting mixture was stirred at room temperature for 16 h at 60° C.
  2. temperaturewas cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting residue was seperated between water (50 mL)
  5. washThe organic phase was washed with a concentrated sodium bicarbonate solution
  6. dry with materialdried (anh. sodium sulfate)
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting material was triturated with EtOH
  9. customdried under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-0782bd9d5dfd4e86a5bd400f8190cdf8
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08895549B2

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