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CAS No. : | 194804-85-8 | MDL No. : | MFCD04114097 |
Formula : | C7H5F2NO2 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | NGORASPPURCGPF-UHFFFAOYSA-N |
M.W : | 173.12 | Pubchem ID : | 2762775 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P280-P305+P351+P338-P310 | UN#: | |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | |
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 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; ethyl acetate; | To <strong>[194804-85-8]4-amino-2,3-difluorobenzoic acid</strong> (4.19 mmol, 725 mg) and N-tert-butyl-3(piperazin-1-ylmethyl)benzamide (2.54 mmol, 700 mg) and triethylamine (10.76 mmol, 1.5 mL, 1089 mg) in dichloromethane (30 mL) was added 1-propanephosphonic acid cyclic anhydride (6.75 mmol, 4 mL, 4296 mg, 50% solution in ethyl acetate) dropwise. The mixture was allowed to stir for 2 hours and then ethyl acetate was added, The organic mixture was washed with saturated sodium hydrogen carbonate, water, and saturated sodium chloride. The organic phase was dried with sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (1.28 g), MS (ESI) m/z 431.6 [M+H]+ | |
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; ethyl acetate; for 2.0h; | To <strong>[194804-85-8]4-amino-2,3-difluorobenzoic acid</strong> (4.19mmol, 725mg) and N-tert-butyl-3-(piperazin-1- ylmethyl)benzamide (2.54mmol, 700mg) and triethylamine (10.76mmol, 1.5mL, 1089mg) in dichloromethane (3OmL) was added 1-propanephosphonic acid cyclic anhydride (6.75 mmol, 4ml_, 4296mg, 50% solution in ethyl acetate) dropwise. The mixture was allowed to stir for 2 hours and then ethyl acetate was added. The organic mixture was washed with saturated sodium hydrogen carbonate, water, and saturated sodium chloride. The organic phase was dried with sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (1.28g). MS (ESI) m/z 431.6 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; HATU; In N,N-dimethyl-formamide; at 50.0℃; for 18.0h;Sealed tube; | A mixture of <strong>[194804-85-8]4-amino-2,3-difluorobenzoic acid</strong> (45.0 mg, 0.260 mmol), 4-chloro-2-(4- (3,3,3-trifluoropropyl)piperazin-l-yl)aniline (80 mg, 0.260 mmol), HATU (148 mg, 0.390 mmol) and TEA (0.109 mL, 0.780 mmol) in DMF (1 mL) was heated to 50 C for 18 h in a 5 mL sealed scintillation vial. The mixture was purified by preparative HPLC (10 -95 MeCN/H20) to give the product as white solid. LC/MS m/z = 463.4 [M+H]+; 1H NMR (400 MHz, CD3OD) delta ppm 2.92 (m, 2H), 3.31 (m, 4H), 3.68-3.53 (m, 6H), 6.78 (dd, 7i=72=7.9 Hz, 1H), 7.32 (d, 7 = 8.4 Hz, 1H), 7.42 (s, 1H), 7.66 (dd, 7i= 72=9.1Hz, 1H), 8.44 (d, 7 = 8.6 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20.0℃; | To a stirred solution of<strong>[194804-85-8]4-amino-2,3-difluorobenzoic acid</strong> (CAS: 194804-85-8) (500 mg, 2.89 mmol) in DMF (10 mL) at room temperature were added HOBt (585 mg, 4.34 mmol), EDCI (832 mg, 4.34 mmol), Et;N (1.2 g, 11.56 mmol) and methylamine hydrochloride (MeNH2 HCI) (390 mg, 5.78 mmol). The reaction was stirred at room temperature overnight. The reaction mixture was diluted with water (50 mL) and extracted with EtOAc (50 mL X 3). The combined organic layers were washed with water (50 mL X 3), dried over anhydrous Na2SOx,,filtered and concentrated. The residue was purified by silica gel column chromatography eluted withDCM/MeOH (from 30/1 to 20/1, v/v) to give intermediate 154 (360 mg, 67% yield) as a brown solid. |
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