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

HRID 1435799Notes

Reaction equation

HRID 1435799 reaction equation
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]

Participants

6

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 79118Ethane, azido-HCID 12562546Bromazolam

Product 1

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

Reagents, catalysts & solvents 2

HCID 84538Palladium(2+) acetate--triphenylphosphane (1/2/2)CatalystHCID 6342AcetonitrileSolvent

Procedure

(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 (8mL) was heated to reflux under nitrogen. See, Liu, et al., 1996; Austin, et al., 1981; Heck, 1985. 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=12.5Hz), 5.49 (d, 1H, J=13.0Hz), 7.21-7.68(m,7H), 7.75(dd, 1H, J=8.5Hz, J=1.5Hz); 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.

Workup

  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)

Sources & evidence

ORD record
ord-ef22921ac1954b9bba346c6e1798bf8a
Source dataset
uspto-grants-2009_11
Patent number
US07618958B2

Reaction notes

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