Structure of 35853-55-5
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CAS No. : | 35853-55-5 |
Formula : | C17H8F6N2O |
M.W : | 370.25 |
SMILES Code : | FC(F)(F)C1=NC2=C(C=CC=C2C(F)(F)F)C(=C1)C(=O)C1=NC=CC=C1 |
MDL No. : | MFCD05863551 |
InChI Key : | GZTUXOWPGYDWNO-UHFFFAOYSA-N |
Pubchem ID : | 9951239 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H317-H319 |
Precautionary Statements: | P280-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In diethyl ether; at -78.0℃; for 0.166667h; | Preparation of pyridin-2-yl-2,8-bis(trifluoromethyl)-4-quinolinemethanone To a solution of the amide described above (10 g, 28.4 mmol) in anhydrous ether (100 ml) was added a solution of 2-pyridyl lithium (Pinder et al (J. Med. Chem. 1968, 11, 267)) [formed by addition of 2-bromopyridine (3.3 ml, 34.6 mmol) to a solution of butyl lithium (29.7 ml of a commercial 1.6 M solution, diluted with an equal quantity of ether) at -78C.] at -78 C. Analysis of the reaction by TLC after 10 min showed that no starting material remained. The reaction was allowed to warm to room temperature, then poured into aqueous ammonium acetate, and extracted with ether (2×100 ml), the combined organic layers washed with brine and dried (MgSO4). Filtration through a pad of silica gel using ethyl acetate-hexane (1:1) afforded 9.0 g (84%) of the crude product. This was recrystallised from isopropyl alcohol to give the product as colourless needles, identical to that described in the literature (Hickmann et al; Pinder et al; Ohnmacht et al; and Adam et al. (Tetrahedron 1991, 36, 7609)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13.11 gm(92%) | EXAMPLE 4 Synthesis of [2,8-bis(trifluoromethyl)-4-quinolinyl]-2-pyridinyl-methanone of Formula 1 Nitrile compound (5) (14.52 g, 0.03811 mole), NaOH (20N, aq. 7.45 ml, 0.149 moles), THF (35 ml) and 30% H2O2 (13 ml, 0.1154 mole) added at 20-25 C. and stirred for 1 hour. Work up is same as described in Example 1. Yield=13.11 gm(92%). IR and NMR were identical with those of the product obtained in Example-1. | |
13.04 gm (92.5%) | EXAMPLE 5 Synthesis of [2,8-bis(trifluoromethyl)-4-quinolinyl]-2-pyridinyl-methanone of Formula 1 Repeating the procedure in Example 4 using aqueous tertiary butyl hydroperoxide, 70% (0.0572 mole, 7.36 ml) instead of hydrogen peroxide, Yield=13.04 gm (92.5%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With H2; In oxygen; toluene; | b) A 500 ml autoclave was loaded in a glove box (O2 content<1 ppm) with 14.8 g (40 mmol) of 2-pyridyl 2,8-bis(trifluoromethyl)-4-quinolyl ketone, with the catalyst solution prepared above and with 134 ml of toluene. The hydrogenation was carried out at 60, at a constant pressure of 60 bar H2 and while stirring intensively. After a hydrogenation time of 19 hours the conversion was 100 (TLC). The hydrogenation solution was evaporated on a rotary evaporator at 45/20 mbar. For the crystallization of the product, the residue (13.8 g) was dissolved in 21 ml of hot toluene, cooled slowly to RT and stirred for 16 hours. The crystallization was completed by cooling to 1 and stirring for 3 hours. The yellow crystals were filtered off, washed with cold toluene and dried for 18 hours and 50/20 mbar. There were obtained 12.7 g (92%) of (R)-alpha-(2-pyridyl)-2,8-bis(trifluoromethyl)-4-quinolinemethanol; m.p. 130-131; 91.8% e.e.; [alpha]D20 +17.1 (c=1, MeOH). Two-fold recrystallization from ethanol/water yielded pure (R) enantiomer [(S) isomer not detectable in the GC]; [alpha]D20 =+18.7 (c=1, MeOH); m.p.: 136.5-137.7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With iron(II) chloride tetrahydrate; oxygen; acetic acid; In dimethyl sulfoxide; at 100.0℃; under 760.051 Torr; for 24.0h; | General procedure: Two 10 mL vials were subsequently charged with CuI (0.0095 g, 0.05 mmol, 10 mol %) or FeCl2·4H2O (0.0094 g, 0.05 mmol, 10 mol %), substrate (0.5 mmol), DMSO (1 mL) and acetic acid (0.030 g, 0.5 mmol). The vials were flushed with O2 for 1 min, capped with an aluminum crimp cap/septum and finally stirred at 100 C for 24 h in an oil bath with a balloon filled with O2 through the septum. After cooling to room temperature, the content of the vials was transferred into a separation funnel and the vials were rinsed with dichloromethane (20 mL). Sodium bicarbonate solution (10 mL, sat.) was added and the organic phase was separated. The aqueous phase was extracted twice with dichloromethane (10 mL). The combined organic fractions were washed with brine (20 mL), dried over MgSO4 and filtered over a pad of Celite. The solvent was removed under reduced pressure and the resulting residue was purified by column chromatography with an automated chromatography system using a silica flash cartridge (40 g) applying a heptane/ethyl acetate gradient (from 100% heptane to 100% ethyl acetate in 25 minutes, 25 mL/min). |
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