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

HRID 75245

反応式

HRID 75245 の反応式
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]

参加物

6

反応物 3

HCID 66111TrimethylsilylacetyleneHCID 79118Ethane, azido-HCID 12562546Bromazolam

生成物 1

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

試薬・触媒・溶媒 2

HCID 84538Palladium(2+) acetate--triphenylphosphane (1/2/2)触媒HCID 6342Acetonitrile溶媒

実験手順

(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.

後処理

  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)

出典と根拠

ORDレコード
ord-3b82a78316ce4dc99556d268b76c8bab
出典データセット
uspto-grants-2014_09
特許番号
US08835424B2

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