Structure of 313348-16-2
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CAS No. : | 313348-16-2 |
Formula : | C16H19N7O6 |
M.W : | 405.37 |
SMILES Code : | O=C(C1=CN(C2=NC(N)=C3N=CN([C@H]4[C@@H]([C@@H]([C@@H](CO)O4)O)O)C3=N2)N=C1)OCC |
* 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 |
---|---|---|
95% | In water; at 30 - 50℃; | A mixture of 2-hydrazino adenosine (100.00 gm), process water (4000.00 mL) and (ethoxy carbonyl) malondialdehyde (55.75 gm) was stirred until reaction mass became clear and filtered immediately through Celite bed, washed bed by process water. Heated filtrate at 45-50° C. until reaction complies (monitored by HPLC). Cooled the reaction mass at 25-30° C. and stirred for 4-5 hours. Filtered the reaction mass and washed with process water (100.00 mL*3). Suction dried well. Dried at 50-60° C. Dry Weight: 115.00 gm-129.50 gm (percent of Yield: -85-95percent). |
With acetic acid; In methanol; | EXAMPLE 1 Ethyl 1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2 -yl}pyrazole-4-carboxylate which can also be identified as 2-(4-ethoxycarbonylpyrazol-1-yl)adenosine (12) To a suspension of 2-hydrazinoadenosine (0.025 g, 0.08 mmol) in a 1:1 mixture of MeOH/AcOH was added <strong>[80370-42-9](ethoxycarbonyl)malondialdehyde</strong> ((0.019 g, 0.12 mmol) and the mixture was heated [heated] at 80° C. for 3 h. The precipitate formed was collected by filtration and washed with EtOH and ether to afford 12. 1H-NMR (DMSO-d6) delta1.25 (t, 3 H), 3.5 (m, 1 H), 3.6 (m, 1 H), 3.8 (d, 1 H), 4.15 (d, 1 H), 4.55 (m, 1H), 5.0 (t, 1 H), 5.2 (d, 1 H), 5.5 (d, 1 H), 5.9 (d, 1H), 7.15-7.3 (m, 5 H), 7.8 (br s, 2 H), 8.1 (s, 1H), 8.4 (s, 1 H), 8.9 (s, 1H). | |
With acetic acid; In methanol; | EXAMPLE 1 Ethyl1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazole-4-carboxylate (12) To a suspension of 2-hydrazinoadenosine (0.025 g, 0.08 mmol) in a 1:1 mixture of MeOH/AcOH was added <strong>[80370-42-9](ethoxycarbonyl)malondialdehyde</strong> ((0.019 g, 0.12 mmol) and the mixture was heated heated at 80° C. for 3 h. The precipitate formed was collected by filtration and washed with EtOH and ether to afford 12. 1H-NMR (DMSO-d6) delta 1.25 (t, 3H), 3.5 (m, 1 H), 3.6 (m, 1H), 3.8 (d, 1H), 4.15 (d, 1H), 4.55 (m, 1H), 5.0 (t, 1H), 5.2 (d, 1H), 5.5 (d, 1H), 5.5 (d, 1H), 5.9 (d, 1H), 7.15-7.3 (m, 5H), 7.8 (br s, 2H), 8.1 (s, 1H), 8.4 (s, 1H,) 8,9(s, 1H). |
In isopropyl alcohol; for 2 - 4h;Heating / reflux; | EXAMPLE 3Preparation of Ethyl 1 - { 9-[Y4S,2R.3R.5RV3 ,4-dihvdroxy-5-fhvdroxymethvnoxolan-2- vn-6-aminopurin-2-yI)pyrazole-4-carboxylate (3)[0062] Ethyl 2-formyl-3-oxopropionate (23 -93g, 0.17 mol) was placed in a flask equipped with mechanical stirrer, gas inlet, gas outlet and reflux condenser. 2-Propanol <n="21"/>was added to the flask followed by 2-hydrazinoadenosine (44.45g, 0.15 raol). The mixture was heated to reflux under stirring for 2-4 hours, following the progress of the reaction by TLC analysis. When the reaction was judged complete, the heat source was removed and the mixture cooled to room temperature. The suspension was cooled under stirring in an ice-bath for 1.5 to 2 hours. The solids were isolated by vacuum filtration, and washed with ice-cold 2-propanol. The product, ethyl l-{9- [(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2- yl}pyrazole-4-carboxylate, was dried under reduced pressure to a constant weight. Yield 54.29g, purity (by HPLC) 96.6percent. | |
In water; at 60 - 65℃; for 4h; | Example 2 Preparation of Pyrazolo Ester from 2-Hydrazino Adenosine 2-hydrazino adenosine (100.00 gm), process water (4000.00 mL) and (ethoxy carbonyl) malondialdehyde (72.73 gm) was taken and stirred. Reaction mass was heated at 60-65° C. and stirred for 4 hours. Cooled the reaction mass to get 25-30° C. and stirred for 1 hour. Filtered the reaction mass and washed with process water (100.00 mL*3). Suck dried well. Dried at 50-55° C. Dry Weight: 130.00 gm-136.00 mum | |
In ethanol; for 2h;Reflux; | Compound 1 (500 mg, 1.56 mmol) was dissolved in ammonia saturated methanol solution, added to a high pressure reaction flask, and stirred at 80 ° C for 7 h.Evaporate the solvent under reduced pressure.The product was purified through silica gel column (dichloromethane: methanol = 9: 1) to give compound 2.The compound 2 (380 mg, 1.25 mmol) was dissolved in 2 ml of hydrazine monohydrate, and the reaction was stirred at room temperature for 10 h, and the unreacted hydrazine was removed by evaporation under reduced pressure.The product was purified by column chromatography over silica gel (dichloromethane: methanol = 5: 1) to afford compound 3.Compound 3 (237 mg, 0.8 mmol) was suspended in 150 ml of ethanol, and methyl 2,2-diformylacetate (149 mg, 1.04 mmol) was added, and the mixture was refluxed for 2 h.The reaction solvent was removed by evaporation under reduced pressure, a yellow solid product was purified by silica gel column chromatography (dichloromethane: methanol = 5: 1) to obtain compound 4;.Compound 4 (202 mg, 0.5 mmol) was suspended in 10 ml of 1 M potassium hydroxide in methanol and stirred at room temperature for 20 h., To give an ester bond cleavage, the organic solvent was distilled off under reduced pressure, the solid was dissolved in ml of water, adjusted to pH 4.0 with 1M HCl, the precipitated solid was filtered, washed with Compound 5. Compound 5 (170 mg, 0.45 mmol), benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate (427 mg, 0.9 mol) and 1-hydroxybenzotriazole (171 mg, 0.9 mol) dissolved in 2 ml of anhydrous DMF,Add 95mul N- tert-butoxycarbonyl group - ethylenediamine, 17H reaction was stirred at room temperature, the solvent was distilled off under reduced pressure, the solid product was recrystallized from methanol to give compound 6.Compound 6 (150 mg, 0.27 mmol) was dissolved in 6 ml of a mixed solution of trifluoroacetic acid and dichloromethane, and stirred at room temperature for 4 h.The solvent was removed under reduced pressure to give the desired product as a white solid, a Reg-NH2 evaporated. | |
In isopropyl alcohol; for 2 - 4h;Heating / reflux; | [0070] Ethyl 2-formyl-3-oxopropionate (23.93g, 0.17 mol) was placed in a flask equipped with mechanical stirrer, gas inlet, gas outlet and reflux condenser. 2-Propanol was added to the flask followed by 2-hydrazinoadenosine (44.45g, 0.15 mol). The mixture was heated to reflux under stirring for 2-4 hours, following the progress of the reaction by TLC analysis. When the reaction was judged complete, the heat source was removed and the mixture cooled to room temperature. The suspension was cooled under stirring in an ice-bath for 1.5 to 2 hours. The solids were isolated by vacuum filtration, and washed with ice-cold 2-propanol. The product, ethyl l-{9- [(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazole-4- carboxylate, was dried under reduced pressure to a constant weight. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In ethanol;Heating / reflux; | [0074] A reaction vessel is charged with 2-hydrazinoadenosine (450 g) and absolute ethanol (11376 g). HCl (7.47 g) and <strong>[80370-42-9]ethyl 2-formyl-3-oxopropionate</strong> (1557 g) are added. The mixture is heated to reflux and sampled until the level of residual 2-hydrazinoadenosine in the mixture is not more than 0.50percent and the level of the compound of formula (3) is not more than 2.5percent. The mixture is slowly cooled to approximately 100C. The product, the compound of formula (4) is isolated by filtration and washed with absolute ethanol (5121 g). The product is dried under vacuum at up to 400C until residual ethanol is not more than 5000 ppm to give ethyl (2E)-3-({9- [(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-[4-(ethoxycarbonyl)- pyrazolyl]purin-6-yl}amino)-2-formylprop-2-enoate.[0075] An elemental analysis of the product of Example 5 A gave the following results: C, 48.75percent; H, 4.86percent; N, 18.05percent; O, 27.57. Theoretical: C, 49.72percent; H, 4.74percent; N, 18.45percent; O, 27.09. The analysis corresponds within experimental error limits to the hemihydrate of the desired product. (C, 48.89percent; H, 4.81percent; N, 18.1percent; O, 28.12)[0076] 1H and 13C NMR spectra were obtained in the following manner. 20.2mg of the compound of formula (4) was dissolved in -0.75 ml of DMSO-d6, and the spectra obtained at ambient temperature on a JEOL ECX-400 NMR spectrometer operating at 400 MHz for 1H and 100 MHz for 13C. The chemical shifts were referenced to the DMSO solvent, 2.50 ppm for 1H and 39.5 ppm for 13C. <n="27"/>RESULTS[0077] The 1H and 13C chemical shifts are listed in Table 1. Two isomers in a ratio of -60/30 were observed in both the 1H and the 13C spectra, labeled as major and minor in the table. <n="28"/>The compound of formula (4) was confirmed to be a mixture of the following two isomers:Major Minor |
Tags: 313348-16-2 synthesis path| 313348-16-2 SDS| 313348-16-2 COA| 313348-16-2 purity| 313348-16-2 application| 313348-16-2 NMR| 313348-16-2 COA| 313348-16-2 structure
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