Structure of 106877-31-0
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 106877-31-0 |
Formula : | C8H8F3N |
M.W : | 175.15 |
SMILES Code : | NC1=CC=C(C(F)(F)F)C(C)=C1 |
MDL No. : | MFCD18399852 |
InChI Key : | YTMVUFIFISNHDB-UHFFFAOYSA-N |
Pubchem ID : | 11019374 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H320-H335 |
Precautionary Statements: | P264-P270-P301+P312-P330 |
* 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 |
---|---|---|
62% | With iron; ammonium chloride; In methanol; water; at 60℃; for 3h; | To intermediate 164b (15.0 g, 73.12 mmol, 1.00 equiv) in methanol/HiQ (100/25 mL) was added elemental Fe (15.0 g, 267.86 mmol, 3.66 equiv) and NH4C1 (1.5.0 g, 280.43 rnmol, 3.83 equiv) and the reaction was stirred at 60 C for 3 h. The mixture was filtered and the filtrate concentrated, diluted with 200 mL of ethyl acetate, washed with 2 x 100 mL of brine, dried over sodium sulfate and then concentrated to afford 8.0 g (62%) of intermediate 164c as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | (4) 3-methyl-4-trifluoromethylaniline (18% yield) deltaF: -58 ppm (broad s) deltaH: 7.37 ppm (1H, d, J:8.5 Hz) 6.43 ppm (2H, m) 2.33 ppm (3H, broad s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | To intennediate 164c (6.0 g, 34,26 mmol, 1 .00 equiv) in water (50 mL) at 0 C was added sulfuric acid (7.06 g, 71.98 mmol, 2.10 equiv) followed by the drop-wise addition of a solution of NaN02 (2.60 g, 37.68 mmol, 1.10 equiv) in water (40 mL) and the mixture was stirred for 1 h. To this was added drop-wise a solution of KI (7.97 g, 48.01 mmol, 1.40 equiv) in water (40 mL) and the reaction was allowed to warm to RT and stirred for 1 h. The mixture was diluted with 200 ml, of ethyl acetate, washed with 2 x 200 ml. of Brine, 1 x 200 mL of aqueous Na^SOa , dried over anhydrous sodium sulfate and concentrated. The residue was purified via silica, gel chromatography (petroleum ether/ethyl acetate, 100:1) to afford 8.2 g (85%) of intermediate 164d as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium hydrogencarbonate; In dichloromethane; water; at 5 - 20℃; for 0.5h; | General procedure: Thiophosgen (114mmol, 1.25equiv.) was added dropwise to a mixture of the respective amine (91mmol, lequiv.) and sodium hydrogen carbonate (318mmol, 3.5equiv.) in dichloromethane (240ml) and water (240ml) at 5C. The reaction medium was vigorously stirred at ambient temperature for 30min. The phases were separated and the water layer was extracted with dichloromethane (50ml). The combined organic layers were dried with Na2SO4 and concentrated under vacuum (not lower than 200mbar at 40C). The obtained isothiocyanate was used directly in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium carbonate; In tetrahydrofuran; at 70℃; for 4h; | General procedure: 2-Chloro-4,6-dimethoxy-1,3,5-triazine (1 mmol) (2), substituted aniline (1 mmol)/heterocyclic amines (3) (1 mmol), anhydrous K2CO3 (2 mmol) were added in dry THF (5 mL) taken in a round bottom flask. The reaction mixture was refluxed at 70 C for 4 h. After completion of the reaction the product is confirmed on thin-layer chromatography (TLC) using eluent (2:8 mL,ethyl acetate-hexane). The reaction mixture was quenched with water and the crude product was extracted with ethyl acetate (3 times) and organic layer was separated and dried over anhydrous Na2SO4. The solvent evaporated on rotavapour. The Crude material was purified by column chromatography (ethylacetate-n-hexane) and product 4(a-x) with good yield (70-75 %) were obtained (Scheme-II). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.8% | With pyridine; In dichloromethane; at 20℃;Inert atmosphere; | 4-Nitrobenzenesulfonyl chloride (1.39 g, 6.28 mmol) and 3-methyl- 4-(trifluoromeihy])aniline (1.00 g, 5.71 mmol) were dissolved in anhydrous methylene chloride (20 mL) at room temperature under argon. Pyridine (1 35 g, 17.13 mmol) was added dropwise via a syringe at room temperature Tire reaction mixture was stirred at room temperature overnight under argon atmosphere. Then, the volatile was removed under reduced pressure. The yellow solid crude was subjected to flash column chromatography (silica gel, CH2CI2) to afford product as a pale yellow solid (1.85 g, 89 8% yield). 1H NMR (400 MHz, DMSO-d6) d 11.15 (s, 1H), 8.40 (d, J = 8 8 Hz, 2H), 8.09 (d, J = 8.8 Hz, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.14 (s, 1H), 7.12 (d, J = 80 Hz, 1H), 224 (s, 3H). |
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