Triethylsilane → Osi-930

HRID 497150Notes

Reaction equation

HRID 497150 reaction equation
[F:1][C:2]([F:20])([F:19])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([C:13]2[S:14][CH:15]=[CH:16][C:17]=2[NH2:18])=[O:12])=[CH:6][CH:5]=1.[N:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]([CH:31]=O)=[CH:23][CH:22]=1.C([SiH](CC)CC)C>FC(F)(F)C(O)=O.ClCCl>[F:20][C:2]([F:19])([F:1])[O:3][C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:11]([C:13]2[S:14][CH:15]=[CH:16][C:17]=2[NH:18][CH2:31][C:24]2[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:21]=[CH:22][CH:23]=2)=[O:12])=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 12052TriethylsilaneHCID 780724-QuinolinecarboxaldehydeHCID 219638853-amino-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide

Product 1

HCID 9868037Osi-930

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

A solution of N-(4-trifluoromethoxyphenyl) 3-aminothiophene-2-carboxamide (1 g, 3.31 mmol) and quinoline-4-carboxaldehyde (347 mg, 2.21 mmol) in trifluoroacetic acid:dichloromethane (1:1, 30 mL) was heated at reflux for 2 h under nitrogen. The reaction was cooled to RT and triethylsilane (0.71 mL, 4.42 mmol) was added. The resulting solution was then stirred at reflux for 16 h under nitrogen. After cooling to RT, the reaction mixture was evaporated under reduced pressure and the residue was partitioned between ethyl acetate (3×100 mL) and saturated sodium bicarbonate solution (50 mL). The organic layers were dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography (20-30% ethyl acetate in hexane) to give EXAMPLE 1 as a light yellow solid, mp: 168-170° C. 1H-NMR (400 MHz/CDCl3):δ=5.01 (d, J=6.2 Hz, 2H), 6.56 (d, J=5.4 Hz, 1H), 7.12 (s, 1H), 7.22 (d, J=8.7 Hz, 2H), 7.25 (s, 1H), 7.44 (d, J=4.3 Hz, 1H), 7.58 (d, J=9.0 Hz, 2H), 7.62 (t, J=8.2 Hz, 1H), 7.76 (t, J=8.3 Hz, 1H), 8.02 (d, J=7.5 Hz, 2H), 8.17 (d, J=8.3 Hz, 1H), 8.86 (d, J=4.5 Hz, 1H). MS (ES+): 444 [MH+]. 13C-NMR (400 MHz/CDCl3): δ=45.9, 101.4, 117.9, 118.9, 119.5, 121.9, 122.0, 122.6, 126.5, 127.2, 129.1, 129.7, 130.6, 136.8, 144.5, 145.4, 148.3, 150.7, 155.9, 163.8. Anal. Calcd for C22H16F3N3O2S: C, 59.59; H, 3.64; N, 9.48; F, 12.85; S, 7.23. Found: C, 59.59; H, 3.67; N, 9.46; F, 13.01; S, 7.23.

Workup

  1. temperatureat reflux for 2 h under nitrogen
  2. temperatureat reflux for 16 h under nitrogen
  3. temperatureAfter cooling to RT
  4. customthe reaction mixture was evaporated under reduced pressure
  5. customthe residue was partitioned between ethyl acetate (3×100 mL) and saturated sodium bicarbonate solution (50 mL)
  6. dry with materialThe organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography (20-30% ethyl acetate in hexane)
  10. customto give EXAMPLE 1 as a light yellow solid, mp: 168-170° C

Sources & evidence

ORD record
ord-057d45d2f5574651af2841cef849cc33
Source dataset
uspto-grants-2005_09
Patent number
US06949563B2

Reaction notes

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