Trimethylsilylacetylene → 6-(2-Fluorophenyl)-4-methyl-8-trimethylsilanylethynyl-4h-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester

HRID 75258Notes

Reaction equation

HRID 75258 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][N:9]2[C:15]=1[CH:14]([CH3:16])[N:13]=[C:12]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[F:23])[C:11]1[CH:24]=[C:25](Br)[CH:26]=[CH:27][C:10]2=1)=[O:5])[CH3:2].[CH3:29][Si:30]([C:33]#[CH:34])([CH3:32])[CH3:31]>C(#N)C.C([O-])(=O)C.[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])(=O)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][N:9]2[C:15]=1[CH:14]([CH3:16])[N:13]=[C:12]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[F:23])[C:11]1[CH:24]=[C:25]([C:34]#[C:33][Si:30]([CH3:32])([CH3:31])[CH3:29])[CH:26]=[CH:27][C:10]2=1)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 685269648-Bromo-6-(2-fluorophenyl)-4-methyl-4h-2,5,10b-triaza-benzo [e]azulene-3-carboxylic acid ethyl ester

Product 1

HCID 685243166-(2-Fluorophenyl)-4-methyl-8-trimethylsilanylethynyl-4h-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl esterYield 79%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 118 (69.3 mg, 0.16 mmol) and bis(triphenylphosphine) palladium (II) acetate (11.68 mg, 0.015 mmol) was dissolved in a mixed solvent system of acetonitrile (120 mL) and TEA (80 mL). The mixture was degassed under vacuum and argon gas was added, after which trimethylsilylacetylene (0.044 mL, 0.31 mmol) was added into the mixture. The mixture was degassed again under vacuum (argon) and heated to reflux. The mixture was heated at reflux until analysis by TLC (EtOAc) indicated that all of the starting material 118 had been consumed. The mixture was cooled to rt and the precipitate which formed was removed by filtration through celite. The filtrate was concentrated under reduced pressure and partitioned between H2O and EtOAc. The combined layers of EtOAc were washed with brine and dried (Na2SO4), after which the solvent was removed under reduced pressure and the residue was purified by flash chromatography (silica gel, EtOAc:hexane 1:1). The conditions for TLC were EtOAc on silica gel. A white solid 119 (58.1 mg, 7 9%) was obtained. mp 186-187° C.; IR (KBr, cm−1) 2410, 2358, 1716, 1497, 1253; 1H NMR (CDCl3) δ 7.92 (s, 1 H), 7.72 (dd, 1.5 Hz, 1 H), 7.6 (t, J=6.9 Hz, 1H), 7.48 (d, J=8.5 Hz, 1 H), 7.42-7.49 (m, 2 H), 7.23-7.29 (m, 1 H), 7.05 (t, J=9.3 Hz, 1 H), 6.71 (q, J=7.3 Hz, 1 H), 4.41 (m, 2 H), 1.42 (t, J=7.1 Hz, 3 H), 1.29 (d, J=7.2, 3 H), 0.24 (s, 9 H). MS (EI) m/e (relative intensity) 459 (M+, 28), 445 (32), 399 (51), 371 (100), 235 (71), 178 (75); [α]26D=−27.8 (c 0.46, EtOAc).

Workup

  1. customThe mixture was degassed under vacuum and argon gas
  2. additionwas added
  3. customThe mixture was degassed again under vacuum (argon)
  4. temperatureheated to reflux
  5. temperatureThe mixture was heated
  6. temperatureat reflux until analysis by TLC (EtOAc)
  7. customhad been consumed
  8. customthe precipitate which formed
  9. customwas removed by filtration through celite
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. custompartitioned between H2O and EtOAc
  12. washThe combined layers of EtOAc were washed with brine
  13. dry with materialdried (Na2SO4)
  14. customafter which the solvent was removed under reduced pressure
  15. customthe residue was purified by flash chromatography (silica gel, EtOAc:hexane 1:1)

Sources & evidence

ORD record
ord-b4d280d84e31457cb76464e6aeb73cad
Source dataset
uspto-grants-2014_09
Patent number
US08835424B2

Reaction notes

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