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CAS No. : | 4857-42-5 | MDL No. : | MFCD00464222 |
Formula : | C5H5NO3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HXIYCKAAQPHZBM-UHFFFAOYSA-N |
M.W : | 127.10 | Pubchem ID : | 853085 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-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 |
---|---|---|
90% | A round bottom flask with magnetic stirrer was charged with 3-methyl-isoxazole-5- carboxylic acid ethyl ester (900 mg, 5.8 mmol) in tetrahydrofuran (2.0 mL). To the reaction was added a solution of sodium hydroxide (465 mg, 11.6 mmol) in water (2 mL), followed by methanol (4 mL). The reaction was stirred at room temperature for 18 - 20 hours under an argon atmosphere. The reaction was transferred to a separatory funnel and the pH adjusted to 2 via addition of IN hydrochloric acid. The mixture was extracted with ethyl acetate (3 x 35 mL) and the combined extractions were washed with brine (1 x 50 mL), dried over magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to yield S-methyl-isoxazole-S-carboxylic acid as a white solid (660 mg, 90percent). The solid was used without purification in the next reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With oxalyl dichloride;N-formyldiethylamine; In dichloromethane; at 20℃; for 0.833333h; | <strong>[4857-42-5]3-Methyl-5-isoxazolecarboxylic acid</strong> (92 mg) was suspended in dry dichloromethane (2 ml) and treated at 20° C. with oxalyl chloride (0.064 ml) and diethyl formamide (1 drop). Effervescence occurred over ca. 10 mins and after 40 mins stirring at room temperature the solution was added dropwise to a solution of 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine (198 mg) (e.g. which can be as prepared in Intermediate 16) in anhydrous acetonitrile (4 ml). The mixture was treated with DIPEA (0.128 ml) and stirred at room temperature under nitrogen for 15 h. Dichloromethane (50 ml) was added to the reaction mixture and the solution was washed with dilute aqueous sodium chloride solution (2.x.50 ml). The organic phase was separated using a hydrophobic frit (70 ml) and loaded directly onto an SPE cartridge (10 g, aminopropyl) which had been pre-washed with methanol. The cartridge was eluted with methanol (.x.2) and the fractions collected and blown down/evaporated to dryness. The residual gum was dissolved in dichloromethane and purified by SPE cartridge (10 g, silica) on a Flashmaster 2 eluting with a gradient of 0-100percent ethyl acetate in cyclohexane over 40 mins. Two fractions (from two chromatographic peaks) were collected and evaporated separately, and each was purified by mass directed autoprep HPLC. Relevant fractions from each were evaporated to dryness. The two residual gums (125 mg and 48 mg respectively) were combined and purified by SPE cartridge (2 g, aminopropyl) which had been pre-washed with methanol. Elution with methanol (.x.2), collection of methanol, and evaporation to dryness gave the title compound N-[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-3-methyl-5-isoxazolecarboxamide as a white foam (173 mg). LCMS showed MH+=413; TRET=2.20 min. |
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