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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
8-Bromoguanosine is a brominated derivative of guanosine.
Synonyms: 2-Amino-8-bromo-6-hydroxypurine riboside; NSC 174257; NSC 79211
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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 4016-63-1 |
Formula : | C10H12BrN5O5 |
M.W : | 362.14 |
SMILES Code : | O=C1NC(N)=NC2=C1N=C(Br)N2[C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O |
Synonyms : |
2-Amino-8-bromo-6-hydroxypurine riboside; NSC 174257; NSC 79211
|
MDL No. : | MFCD00037985 |
InChI Key : | ASUCSHXLTWZYBA-UMMCILCDSA-N |
Pubchem ID : | 135465599 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
85% | With dmap; triethylamine; In acetonitrile; at 20℃; for 0.5h; | Compound 13 (11.0 g, 30.4 mmol) and 4-dimethylaminopyridine (296.9 mg, 2.4 mmol) were dissolved in 100 mL acetonitrile. After slow addition of triethylamine (16.7 mL, 120.0 mmol) and Ac2O (10.0 mL, 106.3 mmol), the mixture continued to stir at room temperature for 30 min. The reaction was quenched by addition of 5 mL MeOH and then the solvent was evaporated in vacuo. The residue was recrystallized from the mixture of 2-propanol and water (v/v, 1:7) to afford 14 as white powder (12.6 g, 85percent), mp 192-196 °C; 1H NMR (400 MHz, CDCl3): delta 11.70 (1H, s), 6.57 (2H, s), 6.37 (1H, s), 6.02 (1H, d, J = 5.2 Hz), 5.96 (1H, d, J = 3.6 Hz), 4.50 (1H, m), 4.34 (2H, t, J = 6.4 Hz), 2.16 (3H, s), 2.14 (3H, s), 2.03 (3H, s). 13CNMR (100 MHz, CDCl3): delta 170.8, 169.6, 169.5, 157.6, 153.7, 152.3, 121.6, 117.7, 88.4, 79.7, 72.2, 70.4, 62.9, 20.7, 20.6, 20.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | To a solution of prop-2-en-1-ol (120 ml) in DMSO (160 mL, anhydrous) was added sodium hydride (1 lg, 276 mmol) in portions at 0 oC. The mixture was allowed to warm to 25°C with stirring for lh, and then 2-amino-8-bromo-9-((2R,3R,4S,5R)-3,4- dihydroxy-5 -(hydroxymethyl)-tetrahydrofuran-2-yl)- 1H-purin-6(911)-one was added. The mixture was stuffed for 0.5h and then heated to 60°C with stirring for 4 hours. Themixture was allowed to cooled to r.t. and then added to diethyl ether (2.5 L) to give a gray precipitate and purified by reverse phase biotage to give a white solid product(4.8g , 51percent).LC-MS: CP-0007023-020: (ES, nz/z): 340 [M+ Hj |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrazine hydrate; In ethanol; water; at 100℃; for 4h;Microwave irradiation; | 8-Hydrazinoguanosine 3 was prepared following the described procedure[29] in 51% yield and under modified conditions using microwave irradiationin 75% yield. To a solution of hydrazine monohydrate (780 lL,10 mmol, 98% with 64 - 65% hydrazine) in the EtOH/H2O mixture(12.4 mL, 30:1 v/v) <strong>[4016-63-1]8-bromoguanosine</strong> 3 (362 mg, 1 mmol) was added and the suspension was stirred in a borosilicate glass vial at 100 C for 4 h in the microwave cavity. After cooling to 55 C obtained fluffy precipitate was filtered off under argon atmosphere and dried under vacuum protected from light to give 8-hydrazinoguanosine 3 (235.3 mg, 75%) as a light blue powder homogeneous by TLC: mp >237 C dec (lit.[29]>238 C dec;lit.[30]>240 C dec); Rf = 0.5 (CH2Cl2/MeOH 3:1); UV (MeOH): lambdamax/nm 261, log epsilon/dm3mol-1cm-1 3.61; IR (KBr) nu/cm-1: 3421 (s), 2920 (m), 1701(m), 1686 (m), 1678 (m), 1655 (m), 1637 (m), 1601 (m), 1578 (m), 1572(m), 1560 (m), 1555 (w), 1491 (w), 1458 (w), 1419 (w), 1126 (w), 1092 (w),1070 (w), 1041 (w); 1H NMR (DMSO-d6) delta/ppm: 11.00 (bs, 1H, NH-1), 7.31 (bs, 3H, NHNH2), 6.22 (bs, 2H, NH2), 5.70 (d, 1H, J 8.5 Hz, H-1'),5.60 (bs, 1H, OH-5'), 5.21 (bd, 1H, OH-2'(OH-3')), 5.01 (bs, 1H, OH-3'(OH-2')), 4.47 (m, 1 H, H-2'), 4.05 (m, 1 H, H-3'), 3.84 (m, 1 H, H-4'),3.59 (m, 2 H, H-5a', H-5b'); 13C NMR (DMSO-d6) delta/ppm: 155.7 (C-6),153.7 (C-2), 152.3 (C-4), 151.4 (C-8), 112.2 (C-5), 85.9 (C-1'), 85.1 (C-4'),70.7 (C-2'(C-3')), 70.2 (C-3'(C-2')), 61.1 (C-5'). The obtained compound isunstable exposed to air and light. Because of rapid decomposition in solution,crude product is used in the next synthetic step without furtherpurification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With bromine; In water; | To a suspension of guanosine 5 (4.0 g, 14.4 mmol) in water (100 mL) was added bromine (0.8 mL, 14.6 mmol) at such a rate that reaction mixture became colourless between each addition. The addition was stopped when the reaction mixture stayed slightly yellow due to unreacted bromine. The colourless solid was quickly filtered off, washed with 60 mL of cold water and 30 mL of cold acetone, recrystallized from 150 mL of hot water and dried in vacuo for 6 h at 60 C. Yield 4.4 g (11.8 mmol, 85%) of colourless, needle-shaped crystals 13, mp 198-200 C; 1H NMR (400 MHz, DMSO-d6): delta 10.82 (1H, s), 6.50 (2H, s), 5.69 (1H, d, J = 6.4 Hz), 5.45 (1H, d, J = 6.0 Hz), 5.09 (1H,d, J = 5.2 Hz), 5.02 (1H, dd, J = 6.0, 11.6 Hz), 4.92 (1H, t, J= 6.0 Hz), 4.14 (1H, m), 3.86 (1H, m), 3.66 (1H, m), 3.52 (1H, m). 13C NMR (100 MHz, DMSO-d6): delta 155.5, 153.4, 152.0, 121.2, 117.5, 89.7, 85.8, 70.5, 70.3, 62.0. |
51% | With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; In N,N-dimethyl-formamide; at 25℃; for 2.5h; | Typical procedure for the bromination of unprotected nucleosides: DBH (323 mg, 1.13 mmol) was added to a stirred solution of 1d (500 mg, 2.05 mmol) in DMF (5 mL). The resulting pale-yellow solution was stirred at room temperature for 20 minutes or until TLC showed absence of starting material and formation of less polar product. Volatiles were evaporated and the residue was coevaporated with MeCN. The resulting pale solid was crystallized from hot acetone to give 2d (500 mg, 75%) as colorless crystals with data as reported.14 |
15% | With sodium azide; bromoisocyanuric acid monosodium salt; In water; N,N-dimethyl-formamide; at 20℃; for 0.5h; | General procedure: 5'-O-Monomethoxytrityl-N2-phenoxyacetylguanosine (33, 0.138 g, 0.2 mmol) was dissolved inaqueous DMF solution (H2O:DMF 1:4, 5 mL) under stirring. SMBI (1.1 equiv., 0.051 g, 0.22 mmol)was added at r.t. and the mixture stirred. Progress of the reaction was followed by TLC. An additionalamount of the reagent (0.15 equiv., 0.007 g) was added into the reaction mixture after 1.5 h. Oncompletion of the reaction by 2 h, the reaction mixture was filtered, evaporated to dryness underreduced pressure and coevaporated with water (2 × 2 mL). The crude reaction mixture was purified bycolumn chromatography (4%-5% MeOH in DCM, v/v) to afford nucleoside 34 (0.148 g, 96%) in pureform as a white solid.8-Bromo-5'-O-monomethoxytrityl-N2-phenoxyacetylguanosine (34). |
With N-Bromosuccinimide; In water; | (1-1-1) Synthesis of 8-Styrylguanosine (Reference Numeral 6a of the Chem. 11) Ten grams of guanosine (reference numeral 1 in the chem. 11), 7.54 g of N-bromosuccinimide, and 500 mL of water were placed in an eggplant-shaped flask, and the mixture solution thus prepared was stirred for 2 hours at room temperature. After the reaction, resultant precipitate was filtered off to obtain 9.03 g of 8-bromoguanosine (reference numeral 2 in the chem. 11). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
wherein the compound is selected from the group consisting of:...2-Chloroadenosine,9-(beta-D-Ribofuranosyl)purine,8-Bromoadenosine,8-Bromo-2'-deoxyadenosine,8-Bromoguanosine,6-Thioinosine,6-Methylthio-9-(beta-D-ribofuranosyl)purine,6-Chloro-9-(beta-D-ribofuranosyl)purine,... | ||
Even further illustrative of the present invention is a method for inhibiting RNA-dependent RNA viral polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection wherein the compound is selected from...4-amino-7-(2-C-methyl-beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile,4-amino-7-(2-C-methyl-beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxmide,2'-C-methyladenosine,8-amino-2'-C-methyladenosine,8-bromoguanosine,8-aminoguanosine,8-aminoadenosine,4-amino-7-(3-deoxy-beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine,... | ||
Further illustrative of the invention is a method for inhibiting RNA-dependent RNA viral polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection wherein the compound is selected from:...2-amino-5-methyl-7-(2-O-methyl-beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidin4(3H)-one,8-azidoguanosine,8-bromoadenosine,8-aminoadenosine,8-bromoguanosine,3'-deoxy-3'-fluorocytidine,3'-deoxy-3'-fluoroguanosine,2-amino-4-chloro-7-(2-O-methyl-beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidin-5-carbonitrile,... |
Illustrative of the invention is a method for inhibiting RNA-dependent RNA viral polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection wherein the compound is selected from:...8-azidoguanosine,8-aminoguanosine,8-bromoadenosine,8-aminoadenosine,8-bromoguanosine,3'-deoxy-3'-fluorocytidine,3'-deoxy-3'-fluoroguanosine,4-amino-7-(3-deoxy-3-fluoro-beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidin-5-carboxamide,... |