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CAS No. : | 17288-35-6 | MDL No. : | MFCD09955613 |
Formula : | C8H6N2O2 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | KBHQUFPZXCNYKN-UHFFFAOYSA-N |
M.W : | 162.15 | Pubchem ID : | 22612670 |
Synonyms : |
|
Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P280-P305+P351+P338 | 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 |
---|---|---|
82% | 3-Amino-2-chloro-pyridine 4f (150 mg, 1.17 mmol), ethyl pyruvate 8 (0.25 ml, 2.00 mmol), pyridinium p-toluenesulfonate, (73 mg, 0.29 mmol) and tetraethoxy-silane (0.26 ml, 1.18 mmol) were suspended in 0.4 ml pyridine and stirred for 24 h at 20 °C. Afterwards Pd[P(C6H6)3]4 (70 mg, 0.06 mmol) and N,N-dicyclohexylmethylamine (0.35 ml, 2.06 mmol) were added and the reaction mixture was heated in a microwave oven to 160 °C for 20 min. The reaction mixture is diluted with 100 ml dichloromethan and extracted two times with 50 ml of a half saturated aqueous sodium hydrogencarbonat solution. The organic layer was dried with sodium sulfate, the solvent was evaporated under reduced pressure and the crude product was purified using chromatography method P3, yielding 190 mg (1.00 mmol) of 1H-Pyrrolo[3,2-b]pyridine-2-carboxylic acid ethyl ester. The ester was dissolved in 17 ml ethanol and 5 ml water. To this solution lithium hydroxide (120 mg, 5.00 mmol) was added. After 16 h the pH value of the reaction mixture was adjusted to pH 4 and the solvent is evaporated in vacuum. The crude product was purified using an acid ion exchanger (Strata-X-C, Phenomenex), yielding of 155 mg (82percent) of the title compound. Purity by method A1: >95percent; MS (ESI) m/z 163 (M + H)+; 1H NMR (DMSO) delta (ppm) 13.34 (br, 1H), 8.77 (d, J = 5.3 Hz, 1H), 8.53 (d, J = 8.3 Hz, 1H), 7.73 (dd, J = 5.4 Hz, J = 8.3 Hz, 1H), 7.33 (br, 1H); 13C NMR (500 MHz, DMSO) delta (ppm) 161.4 (s), 138.0 (s), 136.1 (s), 135.8 (s), 132.7 (s), 128.6 (s), 119.6 (s), 101.2 (s). | |
With sodium hydroxide; water; for 3h;Heating / reflux; | A suspension of 1H PYRROLO [3,2-b] pyridine-2-carboxylic acid ethyl ester (Preparation 31,0. 34g, 1. 77MMOL) in aqueous sodium hydroxide solution (2M, lOmL) was heated under reflux for 3h and the resulting solution was allowed to cool to rt. The pH was adjusted to 4 by addition of glacial acetic acid. Excess acetic acid was removed in vacuo and the resulting suspension cooled to 0°C and then left standing at rt for 16h. The resulting beige precipitate was collected by filtration and dried to give the title compound as a beige solid. 8H (d6 DMSO): 7.12 (1H, s), 7.23 (1H, dd), 7.79 (1H, d), 8.42 (1H, dd). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; at 80℃; for 12h; | To a mixture of 1H-pyrrolo[3,2-bjpyridine-2-carboxylic acid (5 g, 30.8 mmol, 1 eq) in 50 mL of ethyl alcohol was added H2S04 (15.4 g, 154 mmol, 98percent purity, 5 eq) at 15°C, and the mixture was stirred at 80 °C for 12 hours. To the reaction mixture was added NaOH (15percent in water) to neutralize H2S04 until the pH 7-8. A precipitate formed which was filtered. The filter cakewas washed with 50 mL of water to get the crude product (part 1). The mother liquors were concentrated under reduced pressure and the aqueous phase was extracted with three 20 mL portions of ethyl acetate. The combined organic layers were concentrated under reduced pressure to give a solid (part 2). The mixture of solids from part 1 and part 2 were combined to produce the ethyl ester as a white solid which could be used directly into the next step withoutfurther purification. | |
With sulfuric acid; at 15 - 80℃; for 12h;Inert atmosphere; | A mixture of 1H-pyrrolo [3 ,2-blpyridine-2-carboxylic acid, compound 76 (5.0 g, 30.8 mmol, 1.0 eq) in 50 mL of ethyl alcohol was added H2S04 (15.4 g, 154.1 mmol, 98percent purity, 5.0 eq) at 15°C, and then the mixture was stirred at 80°C for 12 hours.The reaction was monitored by LCMS and allowed to run until complete. To the reaction mixture was added NaOH (15percent in water) to neutralized H2S04 until the pH ?7-8. Some brown solids formed which were filtered and washed with 50 mL of water to isolate the crude product (part 1). The filtrate was concentrated under reduced pressure to remove ethyl alcohol and then the aqueous phase was extracted with three 20 mL portions of ethyl acetate. The combinedorganic layers and part 1 were concentrated under reduced pressure to give 7.9 g of compound77 as a crude white solid. |
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