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CAS No. : | 100124-07-0 | MDL No. : | MFCD01605731 |
Formula : | C12H9BO3S | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | IIENVBUXFRSCLM-UHFFFAOYSA-N |
M.W : | 244.07 | Pubchem ID : | 2734376 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P352-P280-P305+P351+P338 | UN#: | |
Hazard Statements: | H319-H315-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 |
---|---|---|
41% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃; for 24h;Sonication; | Example 2 Synthesis of 2-Phenoxathiin-4-yl-6-morpholin-4-yl-pyran-4-one (5) 2-Chloro-6-morpholin-4-yl-pyran-4-one (3)(863 mg, 4 mmol), <strong>[100124-07-0]phenoxathiin-4-boronic acid</strong> (1.07 g, 4.4 mmol), and ground potassium carbonate (1.1 g, 8 mmol) were suspended in dioxane (10 ml) and degassed (sonication for 5 minutes then saturated with N2). Pd(PPh3)4 (231 mg, 0.2 mmol) was then added and the reaction mixture was then heated at 90 C. for 24 hours under a vigorous stirring and a N2 atmosphere. The solvent was removed in vacuo and the residue was then suspended in water (50 ml) and extracted with ethyl acetate (3*50 ml). The organics were combined, washed with saturated brine and dried over sodium sulphate. The solvent was removed in vacuo and the residue was purified by column chromatography (silica; ethyl acetate:ethanol; 9:1) to give the title compound as a white solid (620 mg, 41%). 1H-NMR (300 MHz, DMSO-d6): δ=3.38 (4H, t, J 5 Hz); 3.71 (4H, t, J 5 Hz); 5.49 (1H, d, J 2 Hz); 6.49 (1H, d, J 2 Hz); 7.06 (1H, dd, J 1 and 8 Hz); 7.26 (4H, m); 7.46 (1H, dd, J 1.5 and 8 Hz); 7.55 (1H, dd, J 1.5 and 8 Hz). m/z (LC-MS, ESP): 380 (M++1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 90℃; for 24h; | N,N-Diethyl-4-(4-phenoxathiinyl-4-piperidinylidenemethyl)- benzamide To a mixture of INTERMEDIATE 5 (0.202 g, 0.448 mmol), 4-PHENOXATHIINYL boronic acid (0.164 g, 0.672 MMOL), toluene (3.6 mL), ethanol (0.84 mL), and 2.0 M NA2CO3 (0.56 mL) in a N2 purged vial was added palladium tetrakistriphenylphosphine (0. 0518 g, 0.045 mmol). The resulting mixture was heated at 90 C for 24 h. The reaction was then concentrated in vacuo and the residue was diluted with water (4 mL) and CH2CI2 (4 mL). The layers were separated, and the aqueous phase was extracted with CH2CI2. The combined organic phases were dried over NA2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel column chromatography eluting with 5: 1 CH2CI2 : EtOAc. The purified product was dissolved in CH2CI2 (10 mL) and trifluoroacetic acid (1 mL) was added. After 1.5 h, the reaction was concentrated in vacuo. The residue was LYOPHILIZED from CH3CN/H20 to give COMPOUND 3 as its trifluoroacetic acid salt (0.250 g, 95%) as a slightly yellow solid. Purity (HPLC): > 99% ; H NMR (400MHZ, CD30D) 8 1.06 (br t, J = 6.9 Hz, 3H), 1.22 (br t, J = 7.2 Hz, 3H), 2.44-2. 58 (m, 2H), 2.63-2. 73 (m, 1 H), 2.74-2. 83 (m, L H), 3.18-3. 28 (m, 5H), 3.31-3. 40 (m, 1 H), 3.52 (br q, J = 7.4 Hz, 2H), 6.75 (dd, J = 1.3 Hz, 7.9 Hz, IH), 6.98-7. 13 (m, 5H), 7.14-7. 17 (M, 1H), 7. 35 (s, 4H). | |
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 90℃; for 24h; | To a mixture of INTERMEDIATE 5 (0.202 g, 0.448 MMOL), 4-phenoxathiinyl boronic acid (0.164 g, 0.672 MMOL), toluene (3.6 mL), ethanol (0.84 mL), and 2.0 M NA2CO3 (0.56 mL) in a N2 purged vial was added palladium tetrakistriphenylphosphine (0. 0518 g, 0.045 MMOL). The resulting mixture was heated at 90 C for 24 h. The reaction was then CONCENTRATED IN VACUO and the residue was diluted with water (4 mL) and CH2CI2 (4 mL). The layers were separated, and the aqueous phase was extracted with CH2CI2. The combined organic phases were dried over NA2SO4, filtered, and CONCENTRATED IN VACUO. The crude product was purified by silica gel column chromatography eluting with 5: 1 CH2CI2 : EtOAc. The purified product was dissolved in CH2CI2 (10 mL) and trifluoroacetic acid (I mL) was added. After 1. 5 h, the reaction was CONCENTRATED IN VACUO. The residue was LYOPHILIZED from CH3CN/H20 to give COMPOUND 3 as its trifluoroacetic acid salt (0.250 g, 95%) as a slightly yellow solid. Purity (HPLC) : > 99% ; H NMR (400MHZ, CD30D) 8 1.06 (br t, J = 6.9 Hz, 3H), 1.22 (br t, J = 7.2 Hz, 3H), 2.44-2. 58 (m, 2H), 2.63-2. 73 (M, 1H), 2.74-2. 83 (m, 1 H), 3.18-3. 28 (m, 5H), 3. 31-3. 40 (m, 1H), 3.52 (br q, J = 7.4 Hz, 2H), 6.75 (dd, J = 1. 3 Hz, 7.9 Hz, 1H), 6.98-7. 13 (m, 5H), 7.14-7. 17 (m, 1 H), 7. 35 (s, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 70℃; for 8h;Inert atmosphere; | 4-phenoxathiinyl boronic acid 18.8g (76.88mmol),methyl-2-bromo-5-chloro-benzoate 18.2g (84.57mmol) and tetrakis triphenylphosphinepalladium0.89g (0.769mmol) were placed in a flask, and under a nitrogen atmosphere, itwas dissolved in tetrahydrofuran 257 ml, and then an aqueous solution 128ml of dissolved potassium carbonate 17g (115.3mmol) was added, and stirred at reflux at 70 Cfor 8 h. After completion of the reaction, it was extracted with ethyl acetate,the extract was dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography using n-hexane / ethyl acetate (9: 1 volume ratio) to obtain intermediate M-22 of the desired compound 23.4 g (91% yield). |
83% | With tetrakis(triphenylphosphine) palladium(0); tetrabutylammomium bromide; potassium carbonate; In water; toluene; at 80℃; for 6h;Inert atmosphere; | 2.7g (11mmol) of phenoxi-4-boronic acid, 2.38g (11mmol) of methyl 2-bromobenzoate, 3.06g (22mmol) of potassium carbonate,A mixture of 0.1278 g (0.1 mmol) of tetrakis (triphenylphosphine) palladium and 0.0357 g (0.1 mmol) of tetrabutylammonium bromide was added to a 100 mL three-necked flask, and a mixed solvent of toluene / water of 20 mL / 10 mL was added to the flask ,After replacing the air in the clean flask with nitrogen, the temperature was raised to 80 C under stirring for 6 hours.The reaction solution was washed with water and dried over anhydrous magnesium sulfate, and the organic phase was distilled under reduced pressure to remove toluene.The obtained solid was recrystallized with ethyl acetate to obtain compound 4-1 (compound4-1) (2.91 g, yield 83%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 70℃; for 8h;Inert atmosphere; | 4 -phenoxathiinyl boronic acid 18.8g (76.88mmol),methyl-2-bromo-5-chloro-benzoate 21.1g (84.57mmol) and tetrakis triphenylphosphinepalladium0.89g (0.769mmol) were placed in a flask, and under a nitrogen atmosphere, itwas dissolved in tetrahydrofuran 257 ml, and then an aqueous solution 128ml of dissolvedpotassium carbonate 17g (115.3mmol) was added, and stirred at reflux at 70 C for 8 h. After completion of the reaction, it was extracted with ethyl acetate,the extract was dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The product was purified by silica gelcolumn chromatography using n- hexane / ethyl acetate (9: 1 volume ratio) to obtain intermediate M-3 of the desired compound 26.1 g (92% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Intermediate 1 (30 g, 145 mmol) was added to 300 mL of tetrahydrofuran (THF) and cooled to -78 C. After that, n-butyllithium (n-BuLi) (72 mL, 180 mmol) was slowly added dropwise over 1 hour while stirring, and the reaction was carried out for 1 hour, followed by raising the temperature to room temperature and reacting for 2 hours. After cooling to -78 C. again, triisopropyl borate (33.8 g, 180 mmol) was slowly charged. After further reaction for 2 hours, the temperature was slowly raised to room temperature and reacted for 4 hours.After the reaction, dilute hydrochloric acid (HCl) was added to terminate the reaction, the aqueous layer and the organic layer were separated, and the organic layer was distilled under reduced pressure and extracted with chloroform (1 L) / water (1 L).The solution was dried over magnesium sulfate, and then the organic layer was distilled under reduced pressure. Hexane was used to manufacture Intermediate 4 (25 g, 68%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | Intermediate 8 (20.0 g, 27 mmol) and Intermediate 4 (6.7 g, 27 mmol) were placed in 200 mL of tetrahydrofuran (THF) under nitrogen atmosphere, stirred and refluxed.After that, potassium carbonate (K2CO3) (7.5 g, 54.5 mmol) was dissolved in 30 mL of water and charged. After sufficiently stirring, tetraphenylphosphine palladium (0.9 g, 0.8 mmol) was charged. After 6 hours of reaction, the temperature was lowered to room temperature and filtered.After the filtrate was extracted with chloroform and water, the organic layer was dried over magnesium sulfate. After that, the organic layer was distilled under reduced pressure and recrystallized with ethyl acetate. The resulting solid was filtered and dried to produce Compound 1 (9.3 g, 54%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Under a nitrogen atmosphere,Intermediate 8A (20.0 g, 27 mmol) and Intermediate 4 (6.7 g, 27 mmol) manufactured by the same method as the synthesis example of the above Intermediate 8 were added to 200 mL of tetrahydrofuran (THF), and the mixture was stirred and refluxed.After that, potassium carbonate (K2CO3) (7.5 g, 54.5 mmol) was dissolved in 30 mL of water and charged. After sufficiently stirring, tetraphenylphosphine palladium (0.9 g, 0.8 mmol) was charged. After 6 hours of reaction, the temperature was lowered to room temperature and filtered.After the filtrate was extracted with chloroform and water, the organic layer was dried over magnesium sulfate. After that, the organic layer was distilled under reduced pressure and then recrystallized with ethyl acetate. The resulting solid was filtered and dried to produce Compound 4 (12.3 g, 71%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | Under a nitrogen atmosphere,Intermediate 8B manufactured by the same method as the synthesis example of the above intermediate 8 was used(20.0 g, 27 mmol) and Intermediate 4 (6.7 g, 27 mmol) were added to 200 mL of tetrahydrofuran, stirred and refluxed.After that, potassium carbonate (K2CO3) (7.5 g, 54.5 mmol) was dissolved in 30 mL of water and charged. After sufficiently stirring, tetraphenylphosphine palladium (0.9 g, 0.8 mmol) was charged. After 6 hours of reaction, the temperature was lowered to room temperature and filtered.After the filtrate was extracted with chloroform and water, the organic layer was dried over magnesium sulfate. After that, the organic layer was distilled under reduced pressure and then recrystallized with ethyl acetate. The resulting solid was filtered and dried to produce compound 5 (7.6 g, 44%). |