* 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.
Reference:
[1] Journal of Organic Chemistry, 2003, vol. 68, # 2, p. 666 - 669
2
[ 16321-99-6 ]
[ 3056-18-6 ]
Yield
Reaction Conditions
Operation in experiment
82%
With chloro-trimethyl-silane; isopentyl nitrite In dichloromethane at 0 - 5℃; for 1 h;
Isoamyl nitrite (165 g, 1.41 mol) was dissolved in methylene chloride (500 mL) and then stirred at 0~5 ° C.Trimethylchlorosilane (76 g, 0.70 mol) was added,Then a solution of compound IV (100 g, 0.234 mol) in DCM was added(500mL) was added dropwise to the above mother liquor, after the addition was complete,Continue to stir the reaction at this temperature for 1 hour,The reaction was completed, saturated sodium sulfite solution, liquid separation,The separated organic phase was washed with aqueous sodium bicarbonate,Washed with saturated saline, and dried over anhydrous sodium sulfate, filtered,The mixture was concentrated under reduced pressure until no solution was distilled off. The residue was recrystallized by adding dichloromethane (100 mL) and n-heptane (350 mL)The resulting yellow solid, Compound V (2,6-dichloro-9- (2 ', 3', 5'-tri-O-acetyl-β-D-ribofuranosyl) purine) 86g, molar yield of 82percent.
Reference:
[1] Journal of Organic Chemistry, 2003, vol. 68, # 2, p. 666 - 669
[2] Canadian Journal of Chemistry, 1981, vol. 59, # 17, p. 2608 - 2611
[3] Patent: CN106397516, 2017, A, . Location in patent: Paragraph 0029; 0030; 0080; 0081; 0082; 0083
[4] Journal of Medicinal Chemistry, 1992, vol. 35, # 24, p. 4557 - 4561
[5] Journal of Organic Chemistry, 2002, vol. 67, # 19, p. 6788 - 6796
[6] Synthesis, 1982, # 8, p. 670 - 672
[7] Journal of Pharmaceutical Sciences, 1994, vol. 83, # 4, p. 525 - 531
[8] Bioorganic and Medicinal Chemistry Letters, 1997, vol. 7, # 24, p. 3085 - 3090
[9] Journal of Labelled Compounds and Radiopharmaceuticals, 1997, vol. 40, p. 85 - 87
[10] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 4, p. 403 - 406
[11] Tetrahedron Letters, 2012, vol. 53, # 11, p. 1358 - 1362
[12] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 2, p. 436 - 447
3
[ 5451-40-1 ]
[ 13035-61-5 ]
[ 3056-18-6 ]
Yield
Reaction Conditions
Operation in experiment
79%
With silica gel 60 In ethyl acetate for 0.5 h; Microwave irradiation
2,6-Dichloropurine (23) (190 mg, 1 mmol) and 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose (318 mg, 1 mmol) were dissolved in EtOAc, then 500 mg of silica gel 60 (200-400 mesh) was added. The mixture was concentrated in vacuo and the dry residue was irradiated for 30 min in a domestic microwave oven (120 W). The residue was purified by flash chromatography on silica gel (EtOAc-hexane, 1:2) to yield 24 as yellowish viscous oil (350 mg, 79percent). 1H NMR (CDCl3) δ2.10 (s, 3H, CH3), 2.14 (s, 3H, CH3), 2.17 (s, 3H, CH3), 4.42 (d, 2H, CH2-5’), 4.50 (q, 1H, H-4’), 5.59 (t, 1H, H-3’), 5.81 (t, 1H, H-2’), 6.24 (d, 1H, H-1’), 8.33 (s, 1H, H-8). 13C NMR (DMSO-d6) δ 20.53, 20.70, 20.95 (3xCH3), 63.06 (CH2-5′), 70.72 (CH-4’), 73.42 (CH-3’), 81.02 (CH-2’), 86.74 (CH-1’), 131.56 (C-5), 144.10 (C-8), 152.44 (C-6), 152.79 (C-4), 153.55 (C-2), 169.56, 169.74, 170.39 (3xCO). MS (ESI+) m/e: 447.5 (percent100) (M), 449.9 (percent50) (M+2), 451.6 (percent17) (M+4).
Reference:
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2005, vol. 44, # 1, p. 196 - 197
[2] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 3, p. 235 - 239
[3] Journal of Medicinal Chemistry, 2012, vol. 55, # 14, p. 6467 - 6477
[4] Nucleosides, nucleotides and nucleic acids, 2002, vol. 21, # 1, p. 73 - 78
4
[ 79999-38-5 ]
[ 3056-18-6 ]
Reference:
[1] Canadian Journal of Chemistry, 1981, vol. 59, # 17, p. 2601 - 2607
[2] Journal of Organic Chemistry, 2010, vol. 75, # 14, p. 4880 - 4883
5
[ 118-00-3 ]
[ 3056-18-6 ]
Reference:
[1] Journal of Labelled Compounds and Radiopharmaceuticals, 1997, vol. 40, p. 85 - 87
[2] Bioorganic and Medicinal Chemistry Letters, 1997, vol. 7, # 24, p. 3085 - 3090
[3] Journal of Pharmaceutical Sciences, 1994, vol. 83, # 4, p. 525 - 531
[4] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 2, p. 436 - 447
6
[ 6979-94-8 ]
[ 3056-18-6 ]
Reference:
[1] Journal of Labelled Compounds and Radiopharmaceuticals, 1997, vol. 40, p. 85 - 87
[2] Bioorganic and Medicinal Chemistry Letters, 1997, vol. 7, # 24, p. 3085 - 3090
[3] Journal of Pharmaceutical Sciences, 1994, vol. 83, # 4, p. 525 - 531
[4] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 2, p. 436 - 447
7
[ 30571-54-1 ]
[ 5451-40-1 ]
[ 3056-18-6 ]
Reference:
[1] Patent: US5256650, 1993, A,
8
[ 16321-99-6 ]
[ 5987-73-5 ]
[ 3056-18-6 ]
[ 40896-58-0 ]
Reference:
[1] Journal of Organic Chemistry, 2003, vol. 68, # 2, p. 666 - 669
9
[ 5383-06-2 ]
[ 3056-18-6 ]
Reference:
[1] Canadian Journal of Chemistry, 1981, vol. 59, # 17, p. 2601 - 2607
10
[ 79999-37-4 ]
[ 3056-18-6 ]
Reference:
[1] Canadian Journal of Chemistry, 1981, vol. 59, # 17, p. 2601 - 2607
11
[ 58-61-7 ]
[ 3056-18-6 ]
Reference:
[1] Canadian Journal of Chemistry, 1981, vol. 59, # 17, p. 2601 - 2607
12
[ 3056-18-6 ]
[ 13276-52-3 ]
Yield
Reaction Conditions
Operation in experiment
85%
With acetyl chloride In methanol at 0 - 10℃; for 1.5 h; Inert atmosphere
Under a nitrogen atmosphere, to a three-necked flask equipped with a dropping funnel, 450 ml of all-acetyl protected 2,6-dichloropurine (0.1 mole) and anhydrous methanol were added,Stir until the system is completely clear, cooled to 0-10 , acetyl chloride (1.2mol) was slowly added dropwise, the addition was complete, the reaction was continued for 1.5 hours, TLC detection reaction was complete;To the reaction system, solid potassium carbonate was added in portions until pH = 7-8, filtered, the filtrate was concentrated to dryness, water was added,Extracted three times with 250 ml of ethyl acetate, the combined extracts were dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness.Recrystallization by adding 140 ml of isopropanol gave 27.3 g of 2,6-dichloropurine as a white solid in 85percent yield,
In acetonitrile; at 65℃; for 2h;Product distribution / selectivity;
Method B: A mixture of 9-(2,3,5-tri-(9-acetyl-beta-D-ribofuranosyl)-2,6-dichloropurine (1.12 g, 2.5 mmol) and 2-propylimidazole (2.20 g, 20 mmol) was dissolved in CH3CN (30 mL) and stirred at 65 C under N2 for 2 h (reaction complete, TLC). After removal of volatiles, the residue was dissolved in CH2Cl2 (200 mL) and washed (H2O, 3 x 50 mL). The aqueous phase was extracted with CH2Cl2, and the combined organic phase was dried (Na2SO4) and evaporated to dryness. The residue was chromatographed (MeOH/CH2Cl2, 1 :95) to give 9-(2,3,5-tri-O-acetyl-beta-D- ribofuranosyl)-2-chloro-6-(2-propylimidazol-l-yl)purine (977 mg, 93%).
1-[6-cyclopentylamino-9-(3,4-dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-9<i>H</i>-purin-2-yl]-1<i>H</i>-pyrazole-4-carboxylic acid ethylamide[ No CAS ]
1-[6-cyclohexylamino-9-(3,4-dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-9<i>H</i>-purin-2-yl]-1<i>H</i>-pyrazole-4-carboxylic acid methylamide[ No CAS ]
(2S,3S,4R,5R)-3,4-Dihydroxy-5-{2-(4-pyridin-4-yl-pyrazol-1-yl)-6-[(R)-(tetrahydro-furan-3-yl)amino]-purin-9-yl}-tetrahydro-furan-2-carboxylic acid ethylamide[ No CAS ]
(2S,3S,4R,5R)-3,4-Dihydroxy-5-[6-[(R)-(tetrahydro-furan-3-yl)amino]-2-(4-p-tolyl-pyrazol-1-yl)-purin-9-yl]-tetrahydro-furan-2-carboxylic acid ethylamide[ No CAS ]
(2R,3S,4R,5R)-2-Hydroxymethyl-5-{2-(4-quinazolin-2-yl-pyrazol-1-yl)-6-[(R)-(tetrahydro-furan-3-yl)amino]-purin-9-yl}-tetrahydro-furan-3,4-diol[ No CAS ]
2-(1-{9-((2R,3R,4S,5R)-3,4-Dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-6-[(R)-(tetrahydro-furan-3-yl)amino]-9H-purin-2-yl}-1H-pyrazol-4-yl)-isonicotinic acid[ No CAS ]
(2S,3S,4R,5R)-3,4-Dihydroxy-5-{2-(4-quinolin-2-yl-pyrazol-1-yl)-6-[(R)-(tetrahydro-furan-3-yl)amino]-purin-9-yl}-tetrahydro-furan-2-carboxylic acid ethylamide[ No CAS ]
(1-{6-[((3R)-oxolan-3-yl)amino]-9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl}pyrazol-4-yl)-N-[(4-fluorophenyl)methyl]carboxamide[ No CAS ]
(1-{6-[((3R)-oxolan-3-yl)amino]-9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl}pyrazol-4-yl)-N-[(4-chlorophenyl)methyl]carboxamide[ No CAS ]
1-[9-[3,4-bis-(<i>tert</i>-butyl-dimethyl-silanyloxy)-5-(<i>tert</i>-butyl-dimethyl-silanyloxymethyl)-tetrahydro-furan-2-yl]-6-(tetrahydro-furan-3-ylamino)-9<i>H</i>-purin-2-yl]-1<i>H</i>-pyrazole-4-carboxylic acid propylamide[ No CAS ]
1-[9-[3,4-bis-(<i>tert</i>-butyl-dimethyl-silanyloxy)-5-(<i>tert</i>-butyl-dimethyl-silanyloxymethyl)-tetrahydro-furan-2-yl]-6-(tetrahydro-furan-3-ylamino)-9<i>H</i>-purin-2-yl]-1<i>H</i>-pyrazole-4-carboxylic acid benzylamide[ No CAS ]
1-[9-[3,4-bis-(<i>tert</i>-butyl-dimethyl-silanyloxy)-5-(<i>tert</i>-butyl-dimethyl-silanyloxymethyl)-tetrahydro-furan-2-yl]-6-(tetrahydro-furan-3-ylamino)-9<i>H</i>-purin-2-yl]-1<i>H</i>-pyrazole-4-carboxylic acid 4-chloro-benzylamide[ No CAS ]
1-[9-[3,4-bis-(<i>tert</i>-butyl-dimethyl-silanyloxy)-5-(<i>tert</i>-butyl-dimethyl-silanyloxymethyl)-tetrahydro-furan-2-yl]-6-(tetrahydro-furan-3-ylamino)-9<i>H</i>-purin-2-yl]-1<i>H</i>-pyrazole-4-carboxylic acid 4-fluoro-benzylamide[ No CAS ]
Methyl-carbamic acid (2R,3S,4R,5R)-5-{2-chloro-6-[(R)-(tetrahydro-furan-3-yl)amino]-purin-9-yl}-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl ester[ No CAS ]
Methyl-thiocarbamic acid O-((3aR,4R,6R,6aR)-6-{2-chloro-6-[(R)-(tetrahydro-furan-3-yl)amino]-purin-9-yl}-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl) ester[ No CAS ]
Ethyl-thiocarbamic acid O-((3aR,4R,6R,6aR)-6-{2-chloro-6-[(R)-(tetrahydro-furan-3-yl)amino]-purin-9-yl}-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl) ester[ No CAS ]
Imidazole-1-carboxylic acid (3aR,4R,6R,6aR)-6-{2-chloro-6-[(R)-(tetrahydro-furan-3-yl)amino]-purin-9-yl}-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester[ No CAS ]
Imidazole-1-carbothioic acid O-((3aR,4R,6R,6aR)-6-{2-chloro-6-[(R)-(tetrahydro-furan-3-yl)amino]-purin-9-yl}-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl) ester[ No CAS ]
Cyclopentyl-carbamic acid (3aR,4R,6R,6aR)-6-{2-chloro-6-[(R)-(tetrahydro-furan-3-yl)amino]-purin-9-yl}-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester[ No CAS ]
Cyclopentyl-carbamic acid (2R,3S,4R,5R)-5-{2-chloro-6-[(R)-(tetrahydro-furan-3-yl)amino]-purin-9-yl}-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl ester[ No CAS ]
(3aS,4S,6R,6aR)-6-[2-(4-Amino-cyclohexylamino)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid ethylamide[ No CAS ]
{(3aR,4R,6R,6aR)-6-[2-Chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl}-methanol; compound with toluene-4-sulfonic acid[ No CAS ]
(2S,3S,4R,5R)-5-{6-(2,2-Diphenyl-ethylamino)-2-[2-(1H-imidazol-4-yl)-ethylamino]-purin-9-yl}-3,4-dihydroxy-tetrahydro-furan-2-carboxylic acid ethylamide; compound with trifluoro-acetic acid[ No CAS ]
(2S,3S,4R,5R)-5-[2-(4-Amino-cyclohexylamino)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-3,4-dihydroxy-tetrahydro-furan-2-carboxylic acid ethylamide; compound with trifluoro-acetic acid[ No CAS ]
(2S,3S,4R,5R)-5-[6-(2,2-Diphenyl-ethylamino)-2-(2-piperidin-1-yl-ethylamino)-purin-9-yl]-3,4-dihydroxy-tetrahydro-furan-2-carboxylic acid ethylamide; compound with trifluoro-acetic acid[ No CAS ]
With N-ethyl-N,N-diisopropylamine; In methanol; ethanol; isopropyl alcohol;
2-Chloro-N-(tetrahydro-pyran-4-yl)-adenosine A mixture of acetic acid 4R-acetoxy-5R-acetoxymethyl-2R-(2,6-dichloro-purin-9-yl)-tetrahydro-furan-3R-yl ester (10 g), diisopropylethylamine (5.7 ml), and 4-amino tetrahydropyran hydrochloride (2.02 g), in isopropanol (200 ml) was heated at 50° for 4 h. The cooled mixture was evaporated in vacuo, the residue re-dissolved in methanol (200 ml) and ammonia gas bubbled through the solution for 2 h. The mixture was stirred at 22° C. overnight, and evaporated in vacuo to give a brown oily solid. Purification by flash chromatography on silica gel (Merck 9385), eluding with 75:8:1 DCM:EtOH:880 NH3 to 50:8:1 DCM:EtOH:880NH3, gave the title compound as a pale brown oily solid (7.81 g). LC/MS (System B) Rt 2.24 min. Mass spectrum m/z 3.86 [MH+].