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Chemical Structure| 15763-11-8 Chemical Structure| 15763-11-8

Structure of 2-Hydrazinyl-adenosine
CAS No.: 15763-11-8

Chemical Structure| 15763-11-8

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Product Details of [ 15763-11-8 ]

CAS No. :15763-11-8
Formula : C10H15N7O4
M.W : 297.27
SMILES Code : OC[C@@H]1[C@H]([C@H]([C@H](N2C=NC3=C2N=C(NN)N=C3N)O1)O)O
MDL No. :MFCD01320407
InChI Key :BAYFDGKAUSOEIS-UUOKFMHZSA-N
Pubchem ID :10357262

Safety of [ 15763-11-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H361
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Application In Synthesis of [ 15763-11-8 ]

* 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.

  • Downstream synthetic route of [ 15763-11-8 ]

[ 15763-11-8 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 80370-42-9 ]
  • [ 15763-11-8 ]
  • [ 313348-16-2 ]
YieldReaction ConditionsOperation 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.

  • 2
  • [ 80370-42-9 ]
  • [ 15763-11-8 ]
  • ethyl (2Z)-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 [ No CAS ]
  • [ 946390-52-9 ]
YieldReaction ConditionsOperation in experiment
In ethanol; for 2h;Heating / reflux; EXAMPLE 5Preparation of Ethyl f 2EV3 -f i9- IT4S.2R,3R.5IO-3 ,4-dihvdroxy-5-rhvdroxymethylV oxolan-2-yl1-2-r4-(ethoxycarborivpipyrazolyllpurin-6-yl>aminoV2-forrnylprorho-2-enoate[0066] A mixture of 2-hydrazinoadenosine (100 g, 0.34 mol), ethyl 2-formyl-3- oxopropionate (242g, 1.7 mol) and absolute ethanl were charged to a reactor, and the mixture heated to reflux for 2 hours. When the reaction was judged complete, the heat source was removed and the mixture gradually cooled to 5-100C over a period of 3 hours. The slurry was stirred for 30 minutes at this temperature, and the mixture filtered. The solid material was washed with cold (5-100C) absolute ethanol, and then dried under vacuum at a temperature that did not exceed 400C, to provide 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.[0067] An elemental analysis 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; O5 28.12)[0068] 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.
In ethanol; for 2h;Heating / reflux; [0073] A mixture of 2-hydrazinoadenosine (100 g, 0.34 mol), <strong>[80370-42-9]ethyl 2-formyl-3-oxopropionate</strong> (242g, 1.7 mol) and absolute ethanol were charged to a reactor, and the mixture heated to reflux for 2 hours. When the reaction was judged complete, the heat source was removed and the mixture gradually cooled to 5-100C over a period of 3 hours. The slurry was stirred for 30 minutes at this temperature, and the mixture filtered. The solid material was washed with cold (5-100C) absolute ethanol, and then dried under vacuum at a temperature that did not exceed 400C, to provide 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.
  • 3
  • [ 80370-42-9 ]
  • [ 15763-11-8 ]
  • ethyl (2Z)-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 [ No CAS ]
  • [ 946390-52-9 ]
  • [ 313348-16-2 ]
YieldReaction ConditionsOperation 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
  • 4
  • [ 4903-09-7 ]
  • [ 15763-11-8 ]
  • [ 1417176-03-4 ]
YieldReaction ConditionsOperation in experiment
In methanol;Reflux; General procedure: A mixture of 8 or 9 (0.5 mmol) and 1.1 equiv of aromatic aldehyde, sugar aldehyde or ketone in 30 mL methanol were refluxed for 3?15 h till the disappearance of the starting material and the completion of the reaction was determined by TLC using CH2Cl2:MeOH = 3:1 for compounds 3, 10?14 and using n-butanol:CH3COOH:H2O = 2:1:1 for compounds 15?24. In case of aromatic aldehydes, the products were crystallized out on cooling and filtered off, washed with methanol, and dried to give the pure products. Products of sugar aldehyde or ketone were precipitated after concentration under vacuum and the crude product was crystallized by adding ethyl acetate (1 mL) and excess n-hexane. The products were further purified by reverse phase HPLC chromatography to afford the pure product in about 70percent overall yield.
  • 5
  • [ 80370-42-9 ]
  • [ 15763-11-8 ]
  • [ 64-19-7 ]
  • ethyl 1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazole-4-carboxylate acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
30 g In methanol; at 80℃; for 3h; To a suspension of 2-hydrazinoadenosine (25 g, 80 mmol) in a 1:1 mixture of MeOH/AcOH (450 ml) was added<strong>[80370-42-9](ethoxycarbonyl)malondialdehyde</strong> (19 g, 120 mmol) and the mixture was heated at 80°C for 3 h. The precipitate formedwas collected by filtration and washed with ethanol and diethyl ether to afford 30 g (74 mmol; 92percent molar yields) ofcompound (2) as acetate salt.1H-NMR (DMSO-d6) delta 1.25 (t, 3 H), 1.98 (s, 2.3H acetate), 3.58 (m, 1 H), 3.68 (m, 1 H), 3.90 (dd, 1 H), 4.15(dd, 1 H), 4.25 (q, 2H), 4.60 (t, 1 H), 5.0 (bs, 1 H), 5.20 (bs, 1 H), 5.50 (bs, 1 H), 5.90 (d, 1 H), 7.80 (br s, 2 H), 8.08 (s,1 H), 8.4 (s, 1 H), 8.9 (s, 1 H).IR (ATR). cm-1: 3486, 3334, 3195, 2982, 2941, 1712, 1660, 1609, 1489, 1018, 982.MP: 161.4°C.MS (ESI positive): detectable the protonated molecular ion at m/z=406.5
  • 6
  • [ 80370-42-9 ]
  • [ 15763-11-8 ]
  • [ 64-19-7 ]
  • ethyl 1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazole-4-carboxylate acetate salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% In methanol; at 80℃; for 3h; To a suspension of 2-hydrazinoadenosine (25 g, 80 mmol) in a 1:1 mixture of MeOH/AcOH (450 ml) was added <strong>[80370-42-9](ethoxycarbonyl)malondialdehyde</strong> (19 g, 120 mmol) and the mixture was heated at 80°C for 3 h. The precipitate formed was collected by filtration and washed with ethanol and diethyl ether to afford 30 g(74 mmol; 92percent molar yields) of compound (2) as acetate salt.1 H-NMR (DMSO-d6) o 1.25 (t, 3 H), 1.98 (s, 2.3H acetate), 3.58 (m, 1 H), 3.68 (m, 1 H), 3.90 (dd, 1 H),4.15 (dd, 1 H), 4.25 (q, 2H), 4.60 (t, 1H), 5.0 (bs, 1 H), 5.20 (bs, 1 H), 5.50 (bs, 1 H), 5.90 (d, 1H), 7.80 (br s, 2 H), 8.08 (s, 1H), 8.4 (s, 1 H), 8.9 (s, 1H).IR (ATR). cm-1 : 3486, 3334, 3195,2982,2941, 1712, 1660, 1609, 1489, 1018, 982. MP: 161.4°CMS (ESI positive): detectable the protonated molecular ion at m/z=406.5
  • 7
  • [ 56442-17-2 ]
  • [ 15763-11-8 ]
  • (2R,3R,4S,5R)-2-(6-amino-2-(2-((E)-4-((4-fluorobenzyl)oxy)benzylidene)hydrazineyl)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol [ No CAS ]
YieldReaction ConditionsOperation in experiment
34% In methanol; at 80℃; for 0.5h; General procedure: First, 0.5 g of 2-hydrazinoadenosine (11) and different aralkyl or alkylaldehyde compounds (1.1 equivalent) were combined in methanol(30 ml) and heated by microwave at 80 C for 30 min. The crudeproducts (12-13, 17, 19, 21-32, and 35-39) were precipitated frommethanol, and the other products (14-16, 18, 20, 33-34, and 40-43) were purified from the reaction mixture using silica gel column chromatography. All the crude products were further purified by MPLC on reverse phase C18 material to yield the products(12-43).
 

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