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CAS No. : | 871826-12-9 | MDL No. : | MFCD05863878 |
Formula : | C7H8ClF3N2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HVXHWBMLTSDYGK-UHFFFAOYSA-N |
M.W : | 212.60 | Pubchem ID : | 17749874 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 2h; | General procedure: The carboxylic acid 8 is dissolved in DMF and 2 eq. of the corresponding amine component, 1.5 eq. of HATU and 3 eq. of triethylamine are added. The reaction mixture is stirred at rt until TLC and/or LCMS indicate complete consumption of the starting material (2 h), then water is added. The formed precipitate is filtered off, washed with water and dried in a vacuum drying cabinet at 40C. If appropriate, the product is purified by preparative HPLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100 mg | To a tetrahydrofuran (4 mL) solution of the compound (200 mg) produced in Example 33, triphosgene (267 mg) and diisopropylethylamine (156 muL) were added, and the resulting mixture was stirred at room temperature for 20 hours, and then concentrated under reduced pressure. To the resulting residue, tetrahydrofuran (3 mL) was added, and then, <strong>[871826-12-9]1-[5-(trifluoromethyl)-2-pyridinyl]methanamine hydrochloride</strong> (583 mg) () (173 mg) and diisopropylethylamine (176 muL) were added, followed by stirring at room temperature for 20 hours. The reaction mixture was diluted with a saturated aqueous sodium hydrogen carbonate solution, and extraction was performed with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate = 40:60), whereby the title compound having the following physical property values was obtained (100 mg). TLC: Rf 0.29 (hexane:ethyl acetate = 1:1); 1H-NMR (DMSO-d6): delta 1.53, 2.71, 4.50, 7.25, 7.60, 7.67, 8.26, 8.67, 8.91. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.45 g | With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; | To a mixture of Example 234A (0.37 g, 1.727 mmol), (5-(trifluoromethyl)pyridin-2- yl)methanamine, hydrochloric acid (0.459 g, 2.159 mmol), and N-ethyl-N-isopropylpropan-2- amine (1.056 mL, 6.05 mmol) in N,N-dimethylformamide (7.5 mL), 2-(3H-[l ,2,3]triazolo[4,5- Z?]pyridin-3-yl)- l ,l ,3,3-tetramethylisouronium hexafluorophosphate(V) (0.985 g, 2.59 mmol) was added, and the mixture was stirred at ambient temperature overnight. Water was added, and the aqueous phase was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated, and the residue was purified on silica gel (5-100% ethyl acetate in heptane) to give 0.45 g of the title compound. JH NMR (400 MHz, DMSO- ) delta ppm 8.83 (d, J = 2.3 Hz, 1H), 8.64 (t, J = 5.9 Hz, 1H), 8.13 (ddd, J = 21.1 , 8.4, 2.4 Hz, 1H), 7.39 (dd, J = 19.7, 8.3 Hz, 1H), 4.45 (d, J = 5.8 Hz, 2H), 4.20 - 4.03 (m, 2H), 2.38 - 2.21 (m, 8H), 1.15 (td, J = 7.1, 1.8 Hz, 3H); MS (ESI+) m/z 373.4 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | 2- (0257) (Aminomethyl)-5-(trifluoromethyl)pyridine hydrochloride (0.180 g, 0.804 mmol) was neutralized with 1 M NaOH (0.84 mL). The resulting aqueous solution was extracted with CH2CI2 (3 x). The combined organic layers were dried (Na2S04), and concentrated in vacuo to give a yellowish oil that was dissolved in dry DMSO (1.6 mL) and treated with 2,3-difluoro-6-nitroaniline 4a (0.144 g, 0.804 mmol) followed by Et3N (0.12 mL, 0.885 mmol) and L (8 mg, 0.03 mmol, 0.04 equiv). The reaction mixture was heated to 120 C for 30 h, cooled to room temperature, diluted with water (15 mL) and extracted with CH2CI2 (3 x 10 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (Na2S04), filtered and concentrated under reduced pressure. The residue was purified by chromatography on S1O2 (acetone/hexanes, 1:8 to 1:5 to 1:4, containing Et3N(0.2%)) to give 5i (0.20 g, 75 %) as a yellow solid: Mp 138.2-138.5 C; IR (ATR) 3484, 3370, 1629, 1607, 1551, 1482, 1325, 1282, 1251, 1126, 1077, 1018, 755 cm 1; NMR (400 MHz, CDCL) d 8.88 (s, 1 H), 7.95-7.87 (m, 2 H), 7.44 (d, 1 H, 7 = 8.4 Hz), 6.10-6.05 (m, 3 H), 5.72 (br s, 1H), 4.66 (d, 2 H, 7 = 5.6 Hz); 13C NMR (100 MHz, CDCL) d 160.4, 146.5 (q, 7 = 4.0 Hz), 140.7 (d, 7 = 9.0 Hz), 138.1 (d, 7 = 227.0 Hz), 135.3 (d, 7 = 13.0 Hz), 134.2 (q, 7 = 3.5 Hz), 126.0 (q, 7 = 33.0 Hz), 125.6 (d, 7 = 3.0 Hz), 123.7 (d, 7 = 3.0 Hz), 123.5 (q, 7 = 271.0 Hz), 121.3, 100.9 (d, 7 = 3.0 Hz), 47.8; 19F NMR (376 MHz , CDCL) d -62.3 (s, 3 F), -160.5 (s, 1 F); HRMS (HESI) m/z calcd for CI HION402F4 [M+H]+ 330.0813, found 330.0811. |
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