Structure of 855636-38-3
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CAS No. : | 855636-38-3 |
Formula : | C7H5NO3 |
M.W : | 151.12 |
SMILES Code : | O=C(O)C1=CC=NC(C=O)=C1 |
MDL No. : | MFCD18260019 |
InChI Key : | JNVLSIKRVYZKBP-UHFFFAOYSA-N |
Pubchem ID : | 22323727 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-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 |
---|---|---|
To a mixture of (3-oxo-1,3-dihydro-isobenzofuran-1-yI)-phosphonic acid dimethyl ester (i)(0.18 g, 0.77 mmol) and <strong>[855636-38-3]2-formyl-isonicotinic acid</strong> (iic)(0.12 g, 0.77 mmol) in tetrahydrofuran (10 ml) was added triethylamine (0.32 ml, 2.8 mmol). The reaction mixture was stirred at 50C for 4 hours, then allowed to cool down to room temperature. The tetrahydrofuran was evaporated to half its volume, then a 1N HCI solution added until pH 3. Water was added until no more solid crashed out of solution. The white solid was filtered, washed with water, then hexane and recrystallised from acetonitrile. Amount: 0.9 g, m/z [M+1f 268 (90 % purity) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ozone; In methanol; water; at -78℃; | A solution of 2-vinyl-isonicotinic acid in methanol/DCM 1/1 was cooled to -78C and ozone bubbled through it until the solution becomes blue. A stream of nitrogen is then passed through to remove the ozone excess and 1.5 equivalent of methyl sulfide added. The solution was allowed to warm up to room temperature and was concentrated. The product (iic) was then purified by silica flash chromatography |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | -(4-Fluorophenyl)thiazol-5-yl)(pyridin-4-yl)methanol To a solution of diisopropylamine (0.55 mL, 3.9 mmol) in dry THF (10 mL) at -78C was added n-BuLi (2.4 mL, 3.9 mmol) dropwise, and then the mixture was stirred for 30 min to produce LDA. A solution of 2-(4-fluorophenyl)thiazole (0.5 g, 2.79 mmol) in dry THF (10 mL) at -78C was added dropwise to the above LDA solution, and the mixture was stirred for 30 min. To this reaction mixture was added <strong>[855636-38-3]isonicotinaldehyde</strong> (0.298 g, 2.79 mmol) dropwise and the mixture was stirred for 1 hour at -78C. The reaction was quenched with ammonium chloride solution (10 mL), extracted with ethyl acetate (2 x 20 mL), washed with brine solution (20 mL), dried over sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatography (100-200 mesh silica gel; using 10% MeOH in DCM) to obtain 2-(4-fluorophenyl)thiazol-5-yl)(pyridin-4-yl)methanol (0.6 g, 75% yield). 1H NMR (400 MHz, DMSO-d6): delta 8.56 (d, 2H), 7.91(dd, 2H), 7.79 (s, 1H), 7.44 (d, 2H), 7.28 (ds, 2H), 6.71(d, 1H), 6.12 (d, 1H); LC-MS m/z calculated for [M+H]+ 287.06 found 287.02. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26.5% | 3 -(1 -(4-amino-3 -(3 -fluoro-5-hydroxyphenyl)- 1 H-pyrazo lo [3 ,4-d]pyrimidin- 1-yl)ethyl)-4-( 1,2,3 ,6-tetrahydropyridin-4-yl)- 1 H-isochromen- 1-one hydrochloride(example 64, 37 mg, 0.064 mmol), <strong>[855636-38-3]isonicotinaldehyde</strong> (8.89 mg, 0.083 mmol) and DIEA(11.15 tl, 0.064 mmol) were dissolved in DCM (1.23 ml) followed by a spatula tip ofanhydrous Na2SO4, and the mixture stirred rt for 10 mm prior to add AcOH (10.97 jil,0.192 mmol) and NaBH(OAc)3 (27.1 mg, 0.128 mmol). The resulting mixture was stirredfor lh at rt, then quenched with 2M HClaqueous (1 ml), filtered to remove insolublematerials, and the filtrate purified via reverse phase chromatography using a Biotage Cl 8 60g SNAP with a gradient of water and acetonitrile to give (prior to drying a small amount of 1M HClaqueous was added) the title compound (10.6 mg, 26.5 %) as white solid.1H NMR (400 MHz, DMSO-d6) oe ppm 11.56-11.67 (m, br 1H), 10.20-10.34 (m, br 1H), 8.78-8.82 (m, 2H), 8.10-8.30 (m, 2H), 7.74-8.00 (m, 3H), 7.48-7.68 (m, 2H), 6.82-6.97 (m, 2H), 6.67-7.73 (m, 1H), 6.15-7.73 (m, 1H), 6.15-6.35 (m, 1H), 5.97-6.10 (m, 1H), 4.50-4.68 (m, 2H), 3.90-3.97 (m, 3H), 3.35-3.50 (m, 2H), 3.04-3.27 (m, 1H), 2.52-2.68 (m, 1H), 1.8 1-1.99 (m, 3H). UPLC-MS: 2.34 mm, 590.0 [M+H]+, method 6. | |
26.5% | 3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one hydrochloride (example 64, 37 mg, 0.064 mmol), <strong>[855636-38-3]isonicotinaldehyde</strong> (8.89 mg, 0.083 mmol) and DIEA (11.15 mul, 0.064 mmol) were dissolved in DCM (1.23 ml) followed by a spatula tip of anhydrous Na2SO4, and the mixture stirred rt for 10 min prior to add AcOH (10.97 mul, 0.192 mmol) and NaBH(OAc)3 (27.1 mg, 0.128 mmol). The resulting mixture was stirred for 1 h at rt, then quenched with 2M HClaqueous (1 ml), filtered to remove insoluble materials, and the filtrate purified via reverse phase chromatography using a Biotage C18 60 g SNAP with a gradient of water and acetonitrile to give (prior to drying a small amount of 1M HClaqueous was added) the title compound (10.6 mg, 26.5%) as white solid.1H NMR (400 MHz, DMSO-d6) delta ppm 11.56-11.67 (m, br 1H), 10.20-10.34 (m, br 1H), 8.78-8.82 (m, 2H), 8.10-8.30 (m, 2H), 7.74-8.00 (m, 3H), 7.48-7.68 (m, 2H), 6.82-6.97 (m, 2H), 6.67-7.73 (m, 1H), 6.15-7.73 (m, 1H), 6.15-6.35 (m, 1H), 5.97-6.10 (m, 1H), 4.50-4.68 (m, 2H), 3.90-3.97 (m, 3H), 3.35-3.50 (m, 2H), 3.04-3.27 (m, 1H), 2.52-2.68 (m, 1H), 1.81-1.99 (m, 3H). UPLC-MS: 2.34 min, 590.0 [M+H]+, method 6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With selenium(IV) oxide; In 1,4-dioxane; at 110℃; for 24h; | 2-methyl-4-pyridinecarboxylic acid (5.0 g, 36.5 mmol),Selenium dioxide (10.1 g, 91.3 mmol) was added to 250 ml of dioxane, heated to 110 C., and reacted for 24 hours under magnetic stirring. The reaction was completed by TLC. The reaction solution was filtered while hot, and the solvent was evaporated under reduced pressure. The crude product was recrystallized from absolute ethanol and dried in vacuo to give 2-formyl-4-pyridinecarboxylic acid as a white solid in a yield of 72% and a purity of 98%. |
72% | With iodine; dimethyl sulfoxide; at 150℃; for 1h; | 2-Methylisonicotinic acid (10.0 g, 73.0 mmol), iodine (20.3 g, 80.3 mmol) was added to 120 mL of dimethyl sulfoxide, and the mixture was warmed to 150 C, and the mixture was stirred for 1 hour with magnetic stirring. The reaction was completed by TLC, and the reaction solution was cooled to room temperature and poured to 400 mL.In distilled water, the solid was precipitated, suction filtered, and washed with petroleum ether. The obtained crude product was recrystallized from anhydrous ethanol and dried in vacuo to give 2-formyl isoniconic acid, yield 72%, purity 97%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With potassium carbonate; In ethanol; water; at 20℃; for 4h; | The product intermediate and an equivalent amount of potassium carbonate are added to a mixed solution of 10 mL of ethanol and 15 mL of water.An equivalent amount of <strong>[855636-38-3]2-formylisonicotinic acid</strong> was slowly added thereto, and the mixture was stirred at room temperature for 4 hours by TLC.With brine (15mL) was quenched reaction mixture was then extracted with dichloromethane (10mL × 3).The combined extracts were dried over anhydrous magnesium sulfate and filtered.Dry column chromatography, ethyl acetate / methanol (20:1) as eluent, gave 28i. The chemical structure is as follows: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With potassium carbonate; In ethanol; water; at 20℃; for 4h; | The product intermediate and an equivalent amount of potassium carbonate are added to a mixed solution of 10 mL of ethanol and 15 mL of water.An equivalent amount of <strong>[855636-38-3]2-formylisonicotinic acid</strong> was slowly added thereto, and the mixture was stirred at room temperature for 4 hours by TLC.With brine (15mL) was quenched reaction mixture was then extracted with dichloromethane (10mL × 3).The combined extracts were dried over anhydrous magnesium sulfate and filtered.Dry column chromatography, ethyl acetate / methanol (20:1) as eluent to give 28j, the chemical structure is as follows: |