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[ CAS No. 66224-66-6 ]

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CAS No. :66224-66-6 MDL No. :
Formula : C5H5N5 Boiling Point : -
Linear Structure Formula :- InChI Key :-
M.W :135.13 g/mol Pubchem ID :-
Synonyms :

Safety of [ 66224-66-6 ]

Signal Word: Class:
Precautionary Statements: UN#:
Hazard Statements: Packing Group:

Application In Synthesis of [ 66224-66-6 ]

  • Upstream synthesis route of [ 66224-66-6 ]
  • Downstream synthetic route of [ 66224-66-6 ]

[ 66224-66-6 ] Synthesis Path-Upstream   1~54

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Reference: [1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1982, vol. 36, # 10, p. 707 - 712
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Reference: [1] Journal of the American Chemical Society, 2008, vol. 130, # 46, p. 15512 - 15518
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Reference: [1] Journal of the American Chemical Society, 2008, vol. 130, # 46, p. 15512 - 15518
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Reference: [1] Journal of the American Chemical Society, 2008, vol. 130, # 46, p. 15512 - 15518
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Reference: [1] Journal of the American Chemical Society, 2008, vol. 130, # 46, p. 15512 - 15518
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Reference: [1] Journal of the American Chemical Society, 2008, vol. 130, # 46, p. 15512 - 15518
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Reference: [1] Journal of the American Chemical Society, 2008, vol. 130, # 46, p. 15512 - 15518
  • 8
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YieldReaction ConditionsOperation in experiment
0.18 mg With ferric sulfate nonahydrate In water at 80℃; for 24 h; General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
Reference: [1] Biochemistry, 2016, vol. 55, # 19, p. 2806 - 2811
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YieldReaction ConditionsOperation in experiment
0.12 mg With magnesium sulfate In water at 80℃; for 24 h; General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
Reference: [1] Biochemistry, 2016, vol. 55, # 19, p. 2806 - 2811
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YieldReaction ConditionsOperation in experiment
1.6 mg With copper(II) choride dihydrate In water at 80℃; for 24 h; General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
Reference: [1] Biochemistry, 2016, vol. 55, # 19, p. 2806 - 2811
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Reference: [1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
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Reference: [1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
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Reference: [1] Journal of Organic Chemistry, 1966, vol. 31, p. 2035
[2] , Gmelin Handbook: C: MVol.D1, 15.11.11.7, page 224 - 242,
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YieldReaction ConditionsOperation in experiment
66% With caesium carbonate In N,N-dimethyl-formamide at 60℃; for 7 h; Inert atmosphere 6-amino-9-ethyl-9H-purine was synthesized by the addition of ethyl iodide (3.6 ml, 45 mmol) to a white suspension of adenine (5.00 g, 37.0 mmol) and cesium carbonate (14.5 g, 44.4 mmol) in dry DMF (60 ml) under nitrogen.
The suspension was heated at 60 °C for 7 h.
A white solid was filtered off, the yellow solution was quenched with water (5 ml) and the solvents were removed under reduced pressure.
The yellow solid was partially dissolved in CHCl3 and MeOH and the insoluble material was removed by filtration.
Removal of the solvents under reduced pressure resulted in a crude yellow solid that was purified by flash column chromatography (gradient, 2-10percent v/v MeOH in CHCl3).
6-Amino-9-ethyl-9H-purine was isolated as a white solid (3.97 g, 24.3 mmol, 66percent).
Mp 191-194 °C (lit. 192-193 °C,
38
185-187 °C
39
).
The 1H NMR data were consistent with that in the literature.
39
1H NMR (DMSO-d6): 8.14 (s, 1H), 8.13 (s, 1H), 7.16 (br s, 2H), 4.16 (q, J 7.3 Hz, 2H), 1.39 (t, J 7.3 Hz, 3H); 13C NMR (DMSO-d6, 1): 155.9, 152.3, 149.3, 140.4, 118.8, 38.0, 15.3; νmax (DMSO) 3250, 2250, 2120, 1640 cm-1; HRMS m/z [M+H]+ calculated for C7H9N5: 164.0936. Found: 164.0935.
The regioisomer (6-amino-7-ethyl-7H-purine) was also isolated as a white solid (0.60 g, 3.68 mmol, 10percent).
Reference: [1] Tetrahedron, 2013, vol. 69, # 42, p. 8857 - 8864
[2] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 7, p. 2812 - 2822
[3] European Journal of Pharmacology, 2005, vol. 512, # 2-3, p. 157 - 164
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YieldReaction ConditionsOperation in experiment
71% With potassium carbonate In N,N-dimethyl-formamide at 153℃; for 15 h; Potassium carbonate, 5.1 g (37 mmol), was added to a mixture of 1.8 g (7.41 mmol) of diethyl 2-bromoethylphosphonate and 1 g (7.41 mmol) of adenine in 20 mL of DMF. The mixture was refluxed for 15 h, the precipitate of potassium carbonate was filtered off, and the solvent was removed under reduced pressure. The residue was washed with acetone, and the white precipitate was filtered off and dried under reduced pressure (oil pump) until constant weight. Yield 1.6 g (71percent), mp >250°C. IR spectrum, ν,cm–1: 3143 (NH2), 1699 (C=C), 1029 (P=O). 1H NMRspectrum (DMSO-d6), δ, ppm: 1.24 t (6H, CH3, J =7.1 Hz), 2.55 d.t (2H, CH2, J = 18.2, 7.1 Hz), 4.004.09 m (4H, OCH2), 4.53 d.t (2H, CH2, J = 15.8,7.1 Hz), 8.15 s (1H, Harom), 8.24 s (1H, Harom). 31P NMR spectrum (DMSO-d6): δP 27.75 ppm. Mass spectrum: m/z 300.1 [M + H]+. Found, percent: C 44.33; H 5.81; N 23.18; P 10.54. C11H18N5O3P. Calculated, percent:C 44.15; H 6.06; N 23.40; P 10.35. M 299.3. 9-Ethyl-9H-purin-6-amine (2). The filtrate obtained after separation of compound 1 was left to stand for 12 h. The crystalline solid precipitated therefrom was filtered off and dried under reduced pressure (oil pump) until constant weight. Yield 0.1 g (9percent), mp 94-96°C. IR spectrum, ν, cm–1: 3270, 3105 (NH2), 1673 (C=C). 1H NMR spectrum (CDCl3), δ, ppm: 1.10 t(3H, CH3, J = 7.4 Hz), 3.67 q (2H, CH2, J = 7.3 Hz),7.48 s (1H, Harom), 7.53 s (1H, Harom). Mass spectrum: m/z 202 [M + K]+. Found, percent: C 51.68; H 5.70;N 43.17. C7H9N5. Calculated, percent: C 51.52; H 5.56;N 42.92. M 163.
Reference: [1] Russian Journal of Organic Chemistry, 2018, vol. 54, # 6, p. 938 - 942[2] Zh. Org. Khim., 2018, vol. 54, # 6, p. 932 - 935,4
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Reference: [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1983, # 12, p. 1807 - 1814
[2] Journal of the American Chemical Society, 1993, vol. 115, # 17, p. 7636 - 7644
[3] European Journal of Medicinal Chemistry, 2014, vol. 83, p. 455 - 465
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Reference: [1] Dalton Transactions, 2015, vol. 44, # 8, p. 3540 - 3543
[2] Bioorganic and Medicinal Chemistry, 1998, vol. 6, # 5, p. 523 - 533
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Reference: [1] Tetrahedron, 2002, vol. 58, # 30, p. 6047 - 6059
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  • [ 80-40-0 ]
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Reference: [1] Journal of Organic Chemistry, 1980, vol. 45, # 20, p. 3969 - 3974
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Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1994, # 8, p. 1089 - 1098
[2] Journal of the Chemical Society - Series Chemical Communications, 1992, # 6, p. 513 - 514
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YieldReaction ConditionsOperation in experiment
85.7% at 20℃; for 3 h; Adenine (40g) was first added to the flask, liquid bromine (107 ml) was added under mechanical stirring, the addition process was slow, and then stirred at room temperature for 3 hours;After the completion of the reaction, the excess liquid bromine was removed by adding sodium hydrogen sulfite solution, and the reaction liquid was adjusted to neutrality with ammonia water to precipitate a white powdery solid. Filtration, the solid was washed with ice water to give 8-bromo adenine, pale yellow solid 54 g, yield 85.7percent;
74% at 20℃; Example 8Preparation of 2-(3-(6-amino-9-(pent-4-ynyl)-9H-purin-8-ylthio)phenoxy)-N-hydroxyacetamide (Compound 14)Step 8a. 8-Bromo-9H-purin-6-amine (compound 302); Bromine (9.36 g, 58.5 mmol) was added to H2O (25 mL) with stirring, then the compound 301 (1.1 g, 8.1 mmol) was added into the solution. The mixture was stirred at room temperature overnight. The excess bromine was removed and the solvent was evaporated to give compound 302 as a light yellow solid (1.28 g, 74percent). The crude product was used without further purification: LC-MS: 214 [M+1]+.
Reference: [1] Patent: CN108503643, 2018, A, . Location in patent: Paragraph 0023; 0036; 0037; 0038
[2] Patent: US2008/234297, 2008, A1, . Location in patent: Page/Page column 33; 38
[3] Synthetic Communications, 2013, vol. 43, # 11, p. 1469 - 1476
[4] Journal of Medicinal Chemistry, 2009, vol. 52, # 19, p. 5974 - 5989
[5] Collection of Czechoslovak Chemical Communications, 2000, vol. 65, # 7, p. 1126 - 1144
[6] Collection of Czechoslovak Chemical Communications, 2000, vol. 65, # 7, p. 1109 - 1125
[7] Chemistry - An Asian Journal, 2011, vol. 6, # 8, p. 2048 - 2054
[8] Journal of Medicinal Chemistry, 2005, vol. 48, # 8, p. 2892 - 2905
[9] Patent: WO2015/23976, 2015, A2, . Location in patent: Paragraph 0270
[10] Journal of Medicinal Chemistry, 2015, vol. 58, # 9, p. 3922 - 3943
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Reference: [1] Journal of Organic Chemistry, 1981, vol. 46, # 11, p. 2203 - 2207
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YieldReaction ConditionsOperation in experiment
1.6 mg With copper(II) choride dihydrate In water at 80℃; for 24 h; General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
Reference: [1] Biochemistry, 2016, vol. 55, # 19, p. 2806 - 2811
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  • [ 328-42-7 ]
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  • [ 144-62-7 ]
  • [ 113-00-8 ]
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  • [ 56-06-4 ]
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  • [ 57-13-6 ]
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  • [ 18588-61-9 ]
Reference: [1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
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YieldReaction ConditionsOperation in experiment
15% With sodium hydroxide; methylamine In ethanol; water EXAMPLE 15
A solution prepared by absorbing 18.9 g. (0.61 mole) of methylamine into 100 ml. of ethanol, a catalyst prepared by developing 1.35 g. of Raney nickel containing 8percent by weight of nickel, 100 ml. of ethanol and 13.5 g. (0.1 mole) of adenine were placed into an autoclave and the reaction was carried out at 150° C. for 4.5 hours.
After completing the reaction, the ethanol was removed by distillation, and 600 ml. of water and then 15 g. of a 20percent by weight aqueous solution of sodium hydroxide were added.
The resultant was heated under reflux to dissolve the reaction product and the insoluble material was filtered off under heating.
After cooling, the filtrate was neutralized with sulfuric acid to precipitate crystals.
The precipitate was filtered, washed with water and dried at 70° C. for 15 hours to give 14.2 g. of N6 -methyladenine The purity was 15.5percent by weight and the yield was 15percent.
Reference: [1] Patent: US4900826, 1990, A,
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Reference: [1] Gazzetta Chimica Italiana, 1987, vol. 117, # 6, p. 369 - 374
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Reference: [1] Recueil: Journal of the Royal Netherlands Chemical Society, 1980, vol. 99, # 9, p. 267 - 270
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Reference: [1] Chemical and Pharmaceutical Bulletin, 1996, vol. 44, # 7, p. 1395 - 1399
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Reference: [1] Nucleosides, Nucleotides and Nucleic Acids, 2012, vol. 31, # 12, p. 861 - 871
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  • [ 3083-77-0 ]
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YieldReaction ConditionsOperation in experiment
20% With potassium carbonate In water; N,N-dimethyl-formamide EXAMPLE 26
Synthesis of 9-carboxymethyladenine ethyl ester
Adenine (10 g, 74 mmol) and potassium carbonate (10.29 g, 74 mmol) were suspended in DMF and ethyl bromoacetate (8.24 mL, 74 mmol) was added.
The suspension was stirred for 2.5 h under nitrogen at room temperature and then filtered.
The solid residue was washed three times with DMF (10 mL).
The combined filtrate was evaporated to dryness, in vacuo.
Water (200 mL) was added to the yellowish-orange solid material and the pH adjusted to 6 with 4 N HCl.
After stirring at 0° C. for 10 minutes, the solid was filtered off, washed with water, and recrystallized from 96percent ethanol (150 mL).
The title compound was isolated by filtration and washed thoroughly with ether. Yield: 3.4 g (20percent). M.p. 215.5-220° C. Anal. for C9H11N5O2 found(calc.): C: 48.86(48.65); H: 5.01(4.91); N: 31.66(31.42).
1H-NMR (250 MHz; DMSO-d6): 7.25 (bs, 2H, NH), 5.06 (s, 2H, NCH2), 4.17 (q, 2H, J=7.11 Hz, OCH2) and 1.21 (t, 3H, J=7.13 Hz, NCH2).
13C-NMR. 152.70, 141.30, 61.41, 43.97 and 14.07. FAB-MS. 222 (MH+). IR: Frequency in cm-1 (intensity).
3855 (54.3), 3274(10.4), 3246(14.0), 3117(5.3), 2989(22.3), 2940(33.9), 2876(43.4), 2753(49.0), 2346(56.1), 2106(57.1), 1899(55.7), 1762(14.2), 1742(14.2), 1742(1.0), 1671(1.8), 1644(10.9), 1606(0.6), 1582(7.1), 1522(43.8), 1477(7.2), 1445(35.8) and 1422(8.6).
20% With potassium carbonate In water; N,N-dimethyl-formamide EXAMPLE 26
Synthesis of 9-carboxymethyladenine ethyl ester
Adenine (10 g, 74 mmol) and potassium carbonate (10.29 g, 74 mmol) were suspended in DMF and ethyl bromoacetate (8.24 mL, 74 mmol) was added.
The suspension was stirred for 2.5 h under nitrogen at room temperature and then filtered.
The solid residue was washed three times with DMF (10 mL).
The combined filtrate was evaporated to dryness, in vacuo.
Water (200 mL) was added to the yellowish-orange solid material and the pH adjusted to 6 with 4N HCl.
After stirring at 0° C. for 10 minutes, the solid was filtered off, washed with water, and recrystallized from 96percent ethanol (150 mL).
The title compound was isolated by filtration and washed thoroughly with ether. Yield: 3.4 g (20percent). M.p. 215.5°-220° C. Anal. for C9 H11 N5 O2 found(calc.): C: 48.86(48.65); H: 5.01(4.91); N: 31.66(31.42).
1 H-NMR (250 MHz; DMSO-d6): 7.25 (bs, 2H, NH2), 5.06 (s, 2H, NCH2), 4.17 (q, 2H, J=7.11 Hz, OCH2) and 1.21 (t, 3H, J=7.13 Hz, NCH2).
13 C-NMR. 152.70, 141.30, 61.41, 43.97 and 14.07. FAB-MS. 222 (MH+). IR: Frequency in cm-1: 3855, 3274, 3246, 3117, 2989, 2940, 2876, 2753, 2346, 2106, 1899, 1762, 1742, 1742, 1671, 1644, 1606, 1582, 1522, 1477, 1445 and 1422.
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  • 40
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  • [ 156-81-0 ]
  • [ 849585-22-4 ]
  • [ 617-48-1 ]
  • [ 2491-15-8 ]
  • [ 110-15-6 ]
  • [ 108-53-2 ]
  • [ 71-30-7 ]
  • [ 113-00-8 ]
  • [ 127-17-3 ]
  • [ 66-22-8 ]
  • [ 66224-66-6 ]
  • [ 56-40-6 ]
  • [ 302-72-7 ]
  • [ 18514-52-8 ]
YieldReaction ConditionsOperation in experiment
0.18 mg With ferric sulfate nonahydrate In water at 80℃; for 24 h; General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
Reference: [1] Biochemistry, 2016, vol. 55, # 19, p. 2806 - 2811
  • 41
  • [ 77287-34-4 ]
  • [ 156-81-0 ]
  • [ 849585-22-4 ]
  • [ 617-48-1 ]
  • [ 2491-15-8 ]
  • [ 110-15-6 ]
  • [ 108-53-2 ]
  • [ 71-30-7 ]
  • [ 113-00-8 ]
  • [ 127-17-3 ]
  • [ 66-22-8 ]
  • [ 66224-66-6 ]
  • [ 56-40-6 ]
  • [ 302-72-7 ]
YieldReaction ConditionsOperation in experiment
0.12 mg With magnesium sulfate In water at 80℃; for 24 h; General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
Reference: [1] Biochemistry, 2016, vol. 55, # 19, p. 2806 - 2811
  • 42
  • [ 77287-34-4 ]
  • [ 51953-18-5 ]
  • [ 1455-77-2 ]
  • [ 120-89-8 ]
  • [ 849585-22-4 ]
  • [ 73-40-5 ]
  • [ 328-42-7 ]
  • [ 2491-15-8 ]
  • [ 110-15-6 ]
  • [ 71-30-7 ]
  • [ 120-73-0 ]
  • [ 144-62-7 ]
  • [ 113-00-8 ]
  • [ 127-17-3 ]
  • [ 66-22-8 ]
  • [ 56-06-4 ]
  • [ 66224-66-6 ]
  • [ 57-13-6 ]
  • [ 56-40-6 ]
  • [ 302-72-7 ]
  • [ 18588-61-9 ]
Reference: [1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
  • 43
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  • [ 51953-18-5 ]
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  • [ 849585-22-4 ]
  • [ 73-40-5 ]
  • [ 328-42-7 ]
  • [ 2491-15-8 ]
  • [ 110-15-6 ]
  • [ 71-30-7 ]
  • [ 144-62-7 ]
  • [ 113-00-8 ]
  • [ 127-17-3 ]
  • [ 66-22-8 ]
  • [ 66224-66-6 ]
  • [ 56-40-6 ]
  • [ 18588-61-9 ]
  • [ 18514-52-8 ]
Reference: [1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
  • 44
  • [ 77287-34-4 ]
  • [ 51953-18-5 ]
  • [ 1455-77-2 ]
  • [ 120-89-8 ]
  • [ 73-40-5 ]
  • [ 328-42-7 ]
  • [ 2491-15-8 ]
  • [ 110-15-6 ]
  • [ 71-30-7 ]
  • [ 120-73-0 ]
  • [ 144-62-7 ]
  • [ 113-00-8 ]
  • [ 127-17-3 ]
  • [ 66-22-8 ]
  • [ 66224-66-6 ]
  • [ 57-13-6 ]
  • [ 56-40-6 ]
  • [ 302-72-7 ]
Reference: [1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
  • 45
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  • [ 106941-25-7 ]
Reference: [1] Patent: US2012/238753, 2012, A1,
[2] Patent: CN106699814, 2017, A,
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  • [ 2922-28-3 ]
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Reference: [1] Patent: US2012/238753, 2012, A1,
[2] European Journal of Medicinal Chemistry, 2013, vol. 63, p. 869 - 881
[3] Patent: CN106699814, 2017, A,
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YieldReaction ConditionsOperation in experiment
87% With sodium hydroxide In N,N-dimethyl-formamide at 90 - 140℃; for 12 h; Inert atmosphere To the reaction flask was added 200 ml of N, N-dimethylformamide (DMF)N2 protection,Adenine (30.0 g, 0.222 mol, 1 eq.) Was added,Stirring,NaOH (0.45 g, 0.011 mol) and was addedPropylene carbonate (28.5 g, 0.279 mol, 1.26 eq.),And the temperature was raised to 130 to 140 ° C.12 hours after the sampling test,When the adenine content in 1percent or less,The reaction can be stopped.The temperature slowly reduced to 90 below,200 ml of toluene,Continue to cool to 0 ~ 5 ,And the mixture was stirred for 2 hours.Filtered and dried to give 38.13 g of a white solid,Yield 87percent
87% With sodium hydroxide In N,N-dimethyl-formamide at 130 - 140℃; for 12 h; Inert atmosphere To the reaction flask was added 200 ml of N, N-dimethylformamide (DMF), protected with N2, added adenine (30.0 g, 0.222 mol, 1eq .), stirred, NaOH (0 · 45 g, mol) and R-propylene carbonate (28.5 g, 0. 279 mol, 1.3 eq.) and heated to 130 to 140 ° C. 12 hours after the sampling test, when the adenine content of 1percent or less, can stop the reaction. The temperature slowly drops below 90 ° C, add 200 ml of toluene, continue to cool to 0 ~ 5 ° C and stir for 2 hours. Filtered and dried to give 38.13 g of a white solid, 87percent yield,
81% With sodium hydroxide In N,N-dimethyl-formamide at 140℃; for 16 h; A solution of adenine (3.85g, 28.49 mmol) , (R) - propylene carbonate (2.7 mL, 31.34 mmol), and pulverized sodium hydroxide (60 mg, 1.42 mmol) in anhydrous DMF (80 mL) was heated at 1400C with stirring for 16 h. After cooling, the mixture was then filtered to remove insoluble materials, the filtrate was evaporated under reduced pressure and co-evaporated three times with toluene. The residue was triturated with EtOAc then filtered to give a white solid which was immediately recrystallized in ethanol to afford compound 7 (4.5 g, 81 percent) : mp 193°C (Lit. 192-195°C) ; 1H NMR (DMSO-.d5) δ : 8.15 (s, IH, H-2), 8.06 (s, IH, H-8) , 7.22 (bs, 2H, NH2), 5.06 (bs, IH, OH), 4.06 (m, 3H, CH2N and CHO), 1.12 (d, J = 5.7 Hz, 3H, CH3). 13C NMR (OMSO-d6) δ: 155.87, 152.21, 149.67, 141.44, 118.50, 64.57, 50.07, 20.80. MS (GT, FAB+): 136 (B+1H) \\ 194 (M+1H)+, 216 (MH-Na)+, 232 (M+K) +, 387 (2MH-IH)+.
81%
Stage #1: With potassium carbonate In N,N-dimethyl-formamide at 100 - 120℃; Inert atmosphere
Stage #2: at 120℃; for 8 h;
The Buchi reactor (10 L) was preheated to 150 °C and traces of moisture were blown away with the nitrogen stream. The reactor was filled with argon and cooled down to ~ 70 °C, dry DMF (4 L, ~ 20 ppm of H2O, distilled from P2O5) was added and stirring was switched on (200 rev/min) with heating at 100 °C. When the desired temperature was reached, adenine (A, 150 g, 1 mol) and K2CO3 (72.5 g, 0.525 mol) were added. The reaction temperature was increased to 120 °C. The coarse suspension changed into fine suspension of the potassium salt of adenine and CO2 was being released at the same time. When temperature of 120 °C was reached, carbonate (R)-C (133 g, 1.3 mol) was immediately and quickly added. The reaction mixture was stirred at 120 °C and continuously monitored by TLC. The full conversion was observed at ~ 8 h. The reaction mixture was then cooled to RT and precipitated solid was filtered off, the reactor was rinsed with EtOH, and the solid washed quickly with EtOH (2 x 100 mL). The filtrate was concentrated in vacuo at 60 °C, so that ~ 200 mL of DMF are left in the flask, i.e. ~ 400 mL of solvents were removed. The product usually started to crystallize during the concentration/evaporation process. EtOH (400 mL) was added to the residue and this mixture was sonicated at 70 °C for 2 h to convert the formylated by-product to the desired product 1 and to afford nicely crystallized product 1. After cooling in an ice bath, the product was filtered off, washed (2 x 50 mL iced EtOH), and dried at 60°C for 4 days (under vacuum with P2O5) to give 149 g (72percent) of 1 (98percent purity, HPLC). Repeated experiments afforded up to 81 percent yields of the product 1
72%
Stage #1: With potassium carbonate In N,N-dimethyl-formamide at 100 - 120℃; Inert atmosphere
Stage #2: at 120℃; for 8 h;
The Buchi reactor (10 L) was preheated to 150 °C and traces of moisture were blown away with the nitrogen stream. The reactor was filled with argon and cooled down to ~ 70 °C, dry DMF (4 L, ~ 20 ppm of H2O, distilled from P2O5) was added and stirring was switched on (200 rev/min) with heating at 100 °C. When the desired temperature was reached, adenine (A, 150 g, 1 mol) and K2CO3 (72.5 g, 0.525 mol) were added. The reaction temperature was increased to 120 °C. The coarse suspension changed into fine suspension of the potassium salt of adenine and CO2 was being released at the same time. When temperature of 120 °C was reached, carbonate (R)-C (133 g, 1.3 mol) was immediately and quickly added. The reaction mixture was stirred at 120 °C and continuously monitored by TLC. The full conversion was observed at ~ 8 h. The reaction mixture was then cooled to RT and precipitated solid was filtered off, the reactor was rinsed with EtOH, and the solid washed quickly with EtOH (2 x 100 mL). The filtrate was concentrated in vacuo at 60 °C, so that ~ 200 mL of DMF are left in the flask, i.e. ~ 400 mL of solvents were removed. The product usually started to crystallize during the concentration/evaporation process. EtOH (400 mL) was added to the residue and this mixture was sonicated at 70 °C for 2 h to convert the formylated by-product to the desired product 1 and to afford nicely crystallized product 1. After cooling in an ice bath, the product was filtered off, washed (2 x 50 mL iced EtOH), and dried at 60°C for 4 days (under vacuum with P2O5) to give 149 g (72percent) of 1 (98percent purity, HPLC). Repeated experiments afforded up to 81 percent yields of the product 1
71.8%
Stage #1: With sodium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.333333 h;
Stage #2: at 120℃; for 24.5 h;
40 g (0.296 mol) of adenine To 200 ml of dimethylformamide (DMF)And dissolved 0.94 g (0.0235 mol, 0.08 equiv.) Of sodium hydroxide (NaOH)Followed by stirring at room temperature for 20 minutes39.2 g (0.390 mol, 1.32 Equiv.) Of (R) -propylene carbonate ((R) -propylene carbonate) was added and stirred for 30 minutes.The reaction temperature was 120 [And heated and condensed for 24 hours.Thereafter, the reaction was checked by TLC and HPLC. After the reaction was almost completed (90percent or more), the reaction temperature was cooled to 70 ° C and 240 ml of isopropyl alcohol (IPA) was added to crystallize. Thereafter, the solution was continuously stirred and cooled. The crystals were filtered at 10 ° C, washed with IPA, and dried in a vacuum dryer at 70 ° C to obtain 41 g of HPA (yield: 71.8percent).
71.8%
Stage #1: With sodium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.333333 h;
Stage #2: at 120℃; for 24.5 h;
40 g (0.296 mol) of 6 adenine was dissolved in 200 ml of 7 dimethylformamide (DMF), and 0.94 (0.0235 mol, 0.08 eq.) of 8 sodium hydroxide (NaOH) was added. After 20-min agitation at the room temperature, 39.2 g (0.390 mol, 1.32 eq.) of 9 (R)-propylene carbonate was added and the resultant solution was stirred for 30 minutes. The reaction temperature was elevated to 120° C., and a thermal condensation reaction was activated for 24 hours. Subsequently, the reaction status was examined through TLC and HPLC. After the completion of the reaction (90percent or above), the reaction temperature was reduced to 70° C. and 240 ml of isopropyl alcohol (IPA) was added to active crystallization. Under continuous agitation and cooling, crystals were collected through filtration at 10° C., washed with IPA and then dried out at 70° C. in a low-pressure dryer to obtain 41 g of 5 HPA (yield 71.8percent).
65%
Stage #1: With potassium hydroxide In N,N-dimethyl-formamide at 25 - 30℃; for 0.166667 h;
Stage #2: at 25 - 120℃;
Stage #3: With methanol In N,N-dimethyl-formamide; isopropyl alcohol at 55 - 70℃; for 0.166667 h;
Example 2 (Stage 1 using KOH)Adenine 4 (40 g, 296 mmol, 1.0 eq) and potassium hydroxide (1.66 g, 29.6 mmol, 0.1 eq) were mixed with DMF (190 ml) at 25-30 °C and the mixture was stirred for 10 mm at 25-30 °C. (R)-propylene carbonate 5 (33.6 ml, 39.9 g, 391 mmol, 1.32 eq) was added drop-wise to the reaction mass over10-15 mm at 25-30 °C. The mixture was heated to 120 °C and held at that temperature for 48 h. A clear solution resulted, and the reaction mixture was cooled to 70 °C. A mixture of methanol (120 ml) and iso-propanol (120 ml) was added drop-wise to the reaction mixture over 10 mm, during which time the reaction mixture was allowed to cool to 55 °C, and precipitation of produt was observed. The reaction mixturewas cooled to 5 °C and held at this temperature for I h. The product was isolated by filtration and the cake was washed with a chilled mixture of methanol (10 ml) and isopropanol (10 ml). The resulting solid was dried under vacuum at 70-75 °C, affording HPA 6 as an off-white solid (37 g, 65percent).

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  • 49
  • [ 66224-66-6 ]
  • [ 15448-47-2 ]
  • [ 14047-28-0 ]
YieldReaction ConditionsOperation in experiment
69% With sodium carbonate In N,N-dimethyl-formamide at 95℃; for 6 h; Addition of adenine (200.00 g), sodium carbonate (7.80 g) and DMF (100 ml) was carried out in a dry three-necked flask at room temperature (R) -propylene oxide (150.50 g) was slowly added, followed by reaction at 95 ° C for 6 h. The reaction was cooled to room temperature and toluene (2000 ml) was slowly added. After the addition, the mixture was stirred at 0 ° C Filtered and the filter cake was washed with n-hexane and dried in vacuo to afford 197.20g (69percent yield) (2R)-1-(6-amino-9H-purin-9-yl)propan-2-ol (II)
Reference: [1] Patent: CN103374038, 2016, B, . Location in patent: Paragraph 0037-0039
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  • [ 66224-66-6 ]
  • [ 16606-55-6 ]
  • [ 14047-28-0 ]
YieldReaction ConditionsOperation in experiment
92.9 %Chromat.
Stage #1: With sodium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.333333 h;
Stage #2: at 120 - 130℃; for 16 h;
Step 1: The crude R-9- (2-hydroxypropyl) adenine was obtained100 g of adenine (0.74 mol) and 2.35 g (0.058 mol) of sodium hydroxide were added to 500 mlAnd stirred at room temperature for 20 minutes. 96.5 g (0.946 mol) of R-propylene carbonate was added and the temperature was raised to 120-130 ° C to maintain the temperature of the reaction mixtureShould be 16h;After the completion of the reaction by HPLC, the solution of R-9- (2-hydroxypropyl) adenine which had been reacted was distilled off under reduced pressure for 70 ~80percent of the DMF solvent, adding 300ml toluene, stirring evenly, 0 degrees heat 2h, filtration, drying, in the R-9- (2-hydroxypropyl)The crude product of adenine was 136 g, the crude yield was 95.7percent, the purity was 90.8percent, and the isomer was 8.0percent.Step two: packed column, pretreatmentA 150 g of PRP-6A resin was weighed, poured into a glass column, rinsed three times with ethanol, and the column was compactedNo bubbles, the resin height of 28cm, the cylinder uniform, and then rinse with ethyl acetate 3 times, and finally replaced with ethanol, ethyl acetateTo the test without ethyl acetate so far, the column installed backup.Step 3: LoadingThe crude R-9- (2-hydroxypropyl) adenine 6g dissolved in a small amount of water 20ml, into the PRP-6A resin chromatography column,To the sample solution completely adsorbed to the resin column for the sample is completed.Step 4: Elution80percent ethanol as the eluant, pour into the resin column, with air pump pressure elution, flow controlAt 15 ml / min, the eluent was received in 100 ml portions of the receiver bottle, and the content of the product in each bottle was detected by HPLC.Step 5: ConcentrationThe R-9- (2-hydroxypropyl) adenine and the isomer were collected together under vacuum conditions with a purity of more than 99percentConcentrated to dry, distilled ethanol water recovery applied to get more than 99percent purity of R-9- (2-hydroxypropyl) adenine white crystalline powderAnd 4.7 g of isomer having a purity of more than 99percent, and the chromatographic separation yield was 92.9percent of the product and 97.9percent of the isomer.Step 6: Wash the columnRinse the column with 90percent ethanol in water until no liquid is detected. This indicates that the PRP-6A resin column has been flushedClean, you can continue to use the next time.Step 6: Repeat steps 3 through 6 to cycle through the column 6 timesThe results are shown in Table 1 below:Note: In Table 1 above, the chromatographic separation results were obtained in the longitudinal direction for six times. The yield was chromatographic yield,HPLC area integral purity.
Reference: [1] Patent: CN104892613, 2016, B, . Location in patent: Paragraph 0023; 0024; 0025; 0026; 0027; 0028; 0029-0034
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  • [ 66224-66-6 ]
  • [ 14047-28-0 ]
Reference: [1] Patent: CN103408548, 2016, B,
  • 52
  • [ 24424-99-5 ]
  • [ 66224-66-6 ]
  • [ 309947-86-2 ]
YieldReaction ConditionsOperation in experiment
73% With dmap In tetrahydrofuran at 20℃; for 5 h; Inert atmosphere To a solution of adenine (1.35 g, 10 mmol) and DMAP (122 mg, 1 mmol) in THF (50 mL) under argon was added Boc2O (9.38 g, 43 mmol). The reaction was stirred 5 h at room temperature. After removal of the solvent, EtOAc (400 mL) was added and the solution was washed with HCl 1 N (30 mL) and then with NaCl (3 * 100 mL). After drying over Na2SO4, filtration and removal of the solvents under reduced pressure, the residue was dissolved in methanol (100 mL) and NaHCO3 sat. (45 mL). The reaction was then stirred for 1h30 at 50 °C and after removal of the solvent, water (100 mL) was added. The aqueous phase was then extracted with CHCl3 (2 * 300 mL) and, after drying over Na2SO4, the solvent was removed under reduced pressure. The resulting crude product was purified by flash chromatography (cyclohexane/AcOEt, 10:90) to afford compound 30 (2.44 g, 73percent) as a white solid. 1H NMR (DMSO-d6) δ: 13.69 (s, 1H, NH), 8.80 (s, 1H, H-2), 8.63 (s, 1H, H-8), 1.36 (s, 18H, C(CH3)3) ppm.
Reference: [1] Steroids, 2012, vol. 77, # 12, p. 1177 - 1191,15
[2] Steroids, 2012, vol. 77, # 12, p. 1177 - 1191
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  • [ 309947-86-2 ]
Reference: [1] Tetrahedron, 2007, vol. 63, # 39, p. 9836 - 9841
[2] Journal of Organic Chemistry, 2000, vol. 65, # 22, p. 7697 - 7699
[3] Patent: WO2015/123365, 2015, A1,
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  • [ 66224-66-6 ]
  • [ 202138-50-9 ]
Reference: [1] Organic Process Research and Development, 2010, vol. 14, # 5, p. 1194 - 1201
[2] Patent: WO2015/51874, 2015, A1,
[3] Patent: CN103374038, 2016, B,
[4] Patent: KR2016/135112, 2016, A,
[5] Patent: US2017/354668, 2017, A1,
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