Trimethylsilylacetylene → 8-Trimethylsilylacetylenyl-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]-benzodiazepine

HRID 75245

Reaktionsgleichung

Reaktionsgleichung von HRID 75245
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH3:15])=[N:13][N:14]=[C:10]3[CH2:9][N:8]=[C:7]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:6]=2[CH:22]=1.[CH3:23][Si:24]([C:27]#[CH:28])([CH3:26])[CH3:25].C(N=[N+]=[N-])C>CC([O-])=O.CC([O-])=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd+2].CC#N>[CH3:23][Si:24]([C:27]#[C:28][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH3:15])=[N:13][N:14]=[C:10]3[CH2:9][N:8]=[C:7]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:6]=2[CH:22]=1)([CH3:26])[CH3:25]

Komponenten

6

Edukt 3

HCID 66111TrimethylsilylacetyleneHCID 79118Ethane, azido-HCID 12562546Bromazolam

Produkt 1

HCID 219309408-Trimethylsilylacetylenyl-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]-benzodiazepineAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 84538Palladium(2+) acetate--triphenylphosphane (1/2/2)KatalysatorHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

(XLi269). A mixture of 8 (8-bromo-1-methyl-6-phenyl-4-H-s-triazolo-[4,3-a][1,4]benzodiazepine, 300 mg, 0.85 mmol), trimethylsilylacetylene (208.5 mg, 2.12 mmol) and bis(triphenylphosphine)-palladium (II) acetate in a mixed solvent system of EtN3 (5 mL) and CH3CN (8 mL) was heated to reflux under nitrogen. After stirring for 6 hours at reflux. The mixture was cooled to room temperature. The mixture was concentrated under reduced pressure and H2O (30 mL) was added. The mixture was extracted with CH2Cl2 (3×50 mL). The combined extracts were washed with brine and dried (Na2SO4). After removal of solvent under reduced pressure, the residue was purified by flash chromatography (silica gel, EtOH/EtOAc) to afford benzodiazepine 9 (185 mg, 60% yield) as a white solid: mp 229-233° C.; IR (KBr) 2957, 2156, 1609, 1537, 1491, 1424, 1315, 1249, 881, 844, 750 cm−1; 1H NMR (CDCl3) δ 0.23 (s, 9H), 2.68 (s, 3H), 4.11 (d, 1H, J=12.5 Hz), 5.49 (d, 1H, J=13.0 Hz), 7.21-7.68(m, 7H), 7.75(dd, 1H, J=8.5 Hz, J=1.5 Hz); MS (EI) m/e (relative intensity) 370 (M+, 80), 355 (44), 341 (60), 286 (34), 177 (51), 163 (52) 143 (100), 129 (19), 115 (28). Anal. Calcd. for C22H22N4Si: C, 71.31; H, 5.98; N, 15.12. Found: C, 70.90; H, 5.93; N, 15.08.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureto reflux under nitrogen
  3. temperatureat reflux
  4. concentrationThe mixture was concentrated under reduced pressure and H2O (30 mL)
  5. additionwas added
  6. extractionThe mixture was extracted with CH2Cl2 (3×50 mL)
  7. washThe combined extracts were washed with brine
  8. dry with materialdried (Na2SO4)
  9. customAfter removal of solvent under reduced pressure
  10. customthe residue was purified by flash chromatography (silica gel, EtOH/EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-3b82a78316ce4dc99556d268b76c8bab
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08835424B2

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