Structure of 18225-90-6
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CAS No. : | 18225-90-6 |
Formula : | C6H4FN3 |
M.W : | 137.11 |
SMILES Code : | FC1=CC=C(NN=N2)C2=C1 |
MDL No. : | MFCD00760403 |
InChI Key : | SYGGDXKMRDPIKQ-UHFFFAOYSA-N |
Pubchem ID : | 586225 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-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 |
---|---|---|
33%; 22%; 18% | With potassium carbonate; In tetrahydrofuran; at 20℃; for 16h;Inert atmosphere; | Preparation of compounds 73, 74, and 75. 5-Fluoro-lH-benzo[c/][l,2,3]triazole (112 mg, 0.82 mmol) and potassium carbonate (373 mg, 2.7 mmol) were added to a solution of compound Cll (120 mg, 0.27 mmol) in anhydrous tetrahydrofuran (12 mL) at room temperature under nitrogen and the mixture was stirred for 16 h, at which point TLC analysis of the mixture (2:1 hexanes/ethyl acetate) indicated completion of the reaction. The mixture was diluted with water (80 mL) and extracted with ethyl acetate (3 x 80 mL). The combined organic extracts were washed with saturated aqueous sodium chloride solution (2 x 25 mL), dried with sodium sulfate and filtered. The solvents were removed under reduced pressure and the residue was semi- purified by column chromatography on silica gel, eluting with hexanes/ethyl acetate (3: 1), to provide a mixture of the three regioisomers. The residue was further purified by reverse phase preparative HPLC to provide 73 as a white solid (44 mg, 33%): mp 82-84 C; 1H NMR (500 MHz, CDCL) δ 7.86 (dd, J= 9.0, 4.5 Hz, 1H), 7.46 (dd, J = 9.0, 2.5 Hz, 1H), 7.20 (ddd, J = 9.0, 9.0, 2.0 Hz, 1H), 5.50 (d, Jm = 17.5 Hz, 1H), 5.46 (d, JAB = 17.0 Hz, 1H), 3.54 (d, J = 9.5 Hz, 1H), 3.34 (s, 3H), 3.21 (d, J = 9.0 Hz, 1H), 2.64 (t, J = 9.0 Hz, IH), 2.27-2.18 (m, 1H), 2.18- 2.11 (m, 1H), 1.96-1.88 (m, 2H), 1.83-1.40 (m, 12H), 1.39-1.10 (m, lOH), 0.73 (s, 3H) ppm; ESI MS m/z 496 [M-H]". Further elution provided 75 as a white solid (25 mg, 18%): mp 205-207 C; FontWeight="Bold" FontSize="10" H NMR (500 MHz, CDCI3) δ 7.72-7.68 (m, IH), 7.31-7.27 (m, 2H), 5.43 (d, JAB = 18.0 Hz, 1H), 5.36 (d, JAB = 18.0 Hz, 1H), 3.54 (d, J= 9.0 Hz, 1H), 3.34 (s, 3H), 3.23 (d, J = 9.0 Hz, 1H), 2.70 (t, J = 9.0 Hz, 1H), 2.27-2.18 (m, 1H), 2.18-2.12 (m, IH), 1.97-1.88 (m, 2H), 1.84-1.72 (m, 3H), 1.70-1.58 (m, 3H), 1.57-1.43 (m, 6H), 1.40-1.12 (m, 10H), 0.71 (s, 3H) ppm; ESI MS m/z 498 [M+H]+. Further elution provided 74 as an off-white solid (30 mg, 22%): mp 195-197 C; 1H NMR (500 MHz, CDCI3) δ 8.04 (dd, J = 9.0, 4.5 Hz, IH), 7.15 (dt, J = 9.0, 2.5 Hz, 1H), 6.97 (dd, J = 7.5, 2.0 Hz, IH), 5.40 (d, JAB = 18.0 Hz, IH), 5.33 (d, JAB = 18.0 Hz, IH), 3.54 (d, J = 9.0 Hz, IH), 3.34 (s, 3H), 3.22 (d, J= 9.0 Hz, IH), 2.70 (t, J= 9.0 Hz, IH), 2.27-2.18 (m, IH), 2.18-2.12 (m, IH), 1.97-1.89 (m, 2H), 1.84-1.72 (m, 3H), 1.71-1.57 (m, 3H), 1.57-1.42 (m, 6H), 1.40-1.12 (m, 10H), 0.72 (s, 3H) ppm; ESI MS m/z 498 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12.6% | To a solution of <strong>[18225-90-6]5-fluoro-1H-benzo[d][1,2,3]triazole</strong> (0.20 g, 0.001459 mol) in anhydrous THF (5 mL), which was cooled in an ice water bath under an argon atmosphere, was added sodium hydride (60% dispersion in oil, 0.18 g, 0.004522 mol). After addition, the resulting mixture was stirred for three hours. (R)-3-Bromo-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-2- methylpropanamide (8) (0.51 g, 0.001459 mol) was added to above solution, and the resulting reaction mixture was allowed to stir overnight at room temperature under argon. The reaction was quenched by water, and extracted with ethyl acetate. The organic layer was washed with brine, dried with MgSO4, filtered, and concentrated under vacuum. The product was purified by a silica gel column using hexanes and ethyl acetate (3:1 to 2:1) as eluent to afford 0.075 g (12.6%) of the titled compound as yellowish solid.1H NMR (400 MHz, DMSO-d6) d 10.35 (s, 1H, NH), 8.40 (s, 1H, ArH), 8.19 (d, J = 8.4 Hz, 1H, ArH), 8.10 (d, J = 8.0 Hz, 1H, ArH), 8.07-8.04 (m, 1H, ArH), 7.70 (d, J = 8.2 Hz, 1H, ArH), 7.28-6-7.23 (m, 1H, ArH), 6.45 (s, 1H, OH), 5.05 (d, J = 14.4 Hz, 1H, CH), 4.87 (d, J = 14.4 Hz, 1H, CH), 1.50 (s, 3H, CH3).Mass (ESI, Positive): 430.09 [M+Na]+. |
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