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CAS No. : | 79491-46-6 |
Formula : | C6H4Br2N2O3 |
M.W : | 311.92 |
SMILES Code : | O=[N+](C1=C(Br)N=C(Br)C(OC)=C1)[O-] |
MDL No. : | MFCD18632733 |
InChI Key : | UHFLJHCYEBYJIT-UHFFFAOYSA-N |
Pubchem ID : | 12758208 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 54.95 |
TPSA ? Topological Polar Surface Area: Calculated from | 67.94 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.87 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 2.7 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 2.52 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 1.39 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 0.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 1.82 |
Log S (ESOL):? ESOL: Topological method implemented from | -3.68 |
Solubility | 0.0645 mg/ml ; 0.000207 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -3.78 |
Solubility | 0.0518 mg/ml ; 0.000166 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -3.22 |
Solubility | 0.188 mg/ml ; 0.000601 mol/l |
Class? Solubility class: Log S scale | Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg | High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg | Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) | No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) | Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) | Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) | No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) | No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) | No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from | -6.29 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from | 0.0 |
Ghose? Ghose filter: implemented from | None |
Veber? Veber (GSK) filter: implemented from | 0.0 |
Egan? Egan (Pharmacia) filter: implemented from | 0.0 |
Muegge? Muegge (Bayer) filter: implemented from | 0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat | 0.55 |
PAINS? Pan Assay Interference Structures: implemented from | 0.0 alert |
Brenk? Structural Alert: implemented from | 3.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from | No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) | 2.57 |
* 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 |
---|---|---|
78% | With ammonium hydroxide; at 90℃; for 1.0h;Microwave irradiation; | 5.43 3-Methoxy-5-nitropyridine-2,6-diamine (33) A solution of 32 (0.5 g, 1.6 mmol) in aqueous ammonia (15 M, 12 mL, 180 mmol) was heated at 90 C for 1 h in a microwave oven. The reaction mixture was cooled, the yellow solid was collected by filtration, washed with a small amount of water, and dried under vacuum to afford 33 (230 mg, 78%) as a yellow solid: 1H NMR (400 MHz, DMSO-d6, 393 K) delta = 7.48 (s, 1H), 7.35 (br, 2H), 6.81 (br, 2H), 3.80 (s, 3H); MS ES+ve m/z 185 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With sulfuric acid; nitric acid; at 0 - 65℃; for 2.0h; | Nitric acid (red fuming, 90%; 16 mL, 318 mmol; Aldrich, St. Louis, MO) was added to conc. H2SO4(16 mL) at 0 C, and 2,6-dibromo-3-methoxypyridine (3.4 g, 13 mmol) was added to the resulting solution in portions over 20 min. A reflux condenser was attached to the reaction vessel, and the reaction solution was allowed to warm to ambient temperature before being heated to 65 C for 2 h. The reaction mixture was subsequently poured onto ice in a 500-mL beaker. After the ice melted, the resulting mixture was vacuum filtered, and the collected solid was rinsed with a small amount of water and dried in vacuo to furnish 2,6-dibromo-3-methoxy-5-nitropyridine (1.67 g, 5.4 mmol, 42% yield) as a light-yellow solid. |
31% | With sulfuric acid; nitric acid; potassium nitrate; at 0 - 65℃; | To conc H2SO4 (15 ml) at 0 C were added nitric acid (67%, 4.0 mL) and KNO3 (2.0 g) followed by Compound 137 (2.0 g, 7.5 mmol). The reaction mixture was stirred at 65 C overnight, after which it was poured into crushed ice and neutralized carefully with solid Na2C03, then extracted with EtOAc (2 times). The combined organic extracts were concentrated, and the resulting residue was purified by flash silica gel chromatography (0-80% of EtOAc in hexanes) to give Compound 138 (732 mg, 31% yield). |
28% | With sulfuric acid; nitric acid; at 0 - 65℃; for 36.0h; | 5.42 2,6-Dibromo-3-methoxy-5-nitropyridine (32) Fuming nitric acid (16 M, 5 mL, 80 mmol) was added to a solution of 31 (2.0 g, 7.5 mmol) in sulfuric acid (18 M, 8 mL, 144 mmol) at 0 C, and then the mixture was heated at 65 C for 18 h. Additional concd nitric acid (2.5 mL, 40 mmol) was added and the reaction mixture was stirred at 65 C for a further 18 h. The reaction mixture was cooled and cautiously neutralised with solid sodium carbonate. The resulting mixture was extracted with ethyl acetate (3 * 50 mL), and the combined organic extracts were dried and concentrated under reduced pressure. The residue was purified by chromatography on a silica cartridge (100 g) eluting with a gradient of 0-25% ethyl acetate-cyclohexane over 60 min. The appropriate fractions were combined and evaporated under reduced pressure to give 32 (0.69 g, 28%) as a white solid: 1H NMR (400 MHz, DMSO-d6) delta = 8.24 (s, 1H), 4.00 (s, 3H); LCMS (System A) RT = 1.05 min, 98%, no mass ions observed in either +ve or -ve mode. |
With sulfuric acid; nitric acid; In water; at 0 - 65℃; | E3. 2,6-Dibromo-3-methoxy-5-nitropyridine To 150 ml of concentrated sulfuric acid is added at 0 C 150 ml fuming nitric acid. 40.0 g of 2,6-dibromo-3-methoxypyridine (example E2) is added portionwise to this mixture at 0 C. The reaction mixture is stirred for 45 minutes at 0 C and then heated to 65 C for 2 h. The mixture is poured into 2 l of crushed ice and stored at 0 C overnight. The resulting precipitate is filtered, washed with water and dried under vacuum to yield the title compound. 1H NMR (400 MHz, CDCl3): delta = 4.01 (s, 3H), 7.63 (s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; | Alternate procedures useful for the synthesis of Compound 39 Preparation of 5,7-dibromo-4-methoxy-7-azaindole 36: Vinylmagnesium bromide (0.85 M in THF, 97.7 mL, 83.0 mmol) was added over 30 min. to a stirring solution of <strong>[79491-46-6]2,6-dibromo-3-methoxy-5-nitropyridine</strong> (7.4 g, 23.7 mmol) in THF (160 mL) at -75 C. The solution was stirred 1 h at -75 C., overnight at -20 C., recooled to -75 C. and quenched with saturated aqueous NH4Cl (~100 mL). The reaction mixture was allowed to warm to rt, washed with brine (-100 mL) and extracted with Et2O (150 mL) and CH2Cl2 (2*100 mL). The combined organics were dried (MgSO4), filtered and concentrated. The residue was purified by flash column chromatography (SiO2, 3:1 hexanes/EtOAc) to yield 5,7-dibromo-4-methoxy-7-azaindole 36 (1.10 g, 3.60 mmol, 15%) as a pale yellow solid. | |
In tetrahydrofuran; | Alternate Procedures Useful for the Synthesis of Compound 39 Preparation of 5,7-dibromo-4-methoxy-7-azaindole 36: Vinylmagnesium bromide (0.85 M in THF, 97.7 mL, 83.0 mmol) was added over 30 min. to a stirring solution of <strong>[79491-46-6]2,6-dibromo-3-methoxy-5-nitropyridine</strong> (7.4 g, 23.7 mmol) in THF (160 mL) at -75 C. The solution was stirred 1 h at -75 C., overnight at -20 C., recooled to -75 C. and quenched with saturated aqueous NH4Cl (~100 mL). The reaction mixture was allowed to warm to rt, washed with brine (~100 mL) and extracted with Et2O (150 mL) and CH2Cl2 (2*100 mL). The combined organics were dried (MgSO4), filtered and concentrated. The residue was purified by flash column chromatography (SiO2, 3:1 hexanes/EtOAc) to yield 5,7-dibromo-4-methoxy-7-azaindole 36 (1.10 g, 3.60 mmol, 15%) as a pale yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In methanol; at 20℃; for 1.0h; | To a solution of Compound 138 (200 mg, 0.64 mmol) in anhyd MeOH (6 mL) was added NaOMe (46 mg, 0.85 mmol). The reaction mixture was stirred at room temperature for 1 h and then concentrated under vacuum. The resulting residue was washed with water and filtered. The collected solids were washed with ice cold water and dried under vacuum to give Compound 139 (150 mg, 89% yield). |
In methanol; at 20℃; for 1.0h; | E4. 2-Bromo-5,6-dimethoxy-3-nitropyridine 20 g of <strong>[79491-46-6]2,6-dibromo-3-methoxy-5-nitropyridine</strong> (example E3) are dissolved in 550 ml of anhydrous methanol at 30-40 C. 4.6 g sodium methoxide dissolved in 30 ml anhydrous methanol is added to this solution. The reaction mixture is stirred for one hour at room temperature, poured into 700 ml of water and stored in the refrigerator overnight. The precipitate is filtered, washed with ice cold water and dried under vacuum to yield the title compound. 1H NMR (400 MHz, CDCl3): delta = 3.95 (s, 3H), 4.12 (s, 3H), 7.69 (s, 1 H). 13C NMR (100 MHz, CDCl3): delta = 55.68, 56.73, 115.33, 121.89, 143.18, 155.10. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With sodium methylate; at 20℃; for 16.0h; | Sodium methoxide (0.5M in methanol; 11.4 mL, 5.71 mmol) was added to a slurry of <strong>[79491-46-6]2,6-dibromo-3-methoxy-5-nitropyridine</strong> (34b; 1.62 g, 5.19 mmol) in anhydrous MeOH (20 mL), and the resulting mixture was stirred at ambient temperature for 16 h, then cooled to 0 C and diluted with water (30 mL). The cold mixture was vacuum filtered and the collected solid was rinsed with ice-cold MeOH (10 mL). The collected solid was then dried in vacuo to give 2-bromo-5,6-dimethoxy-3-nitropyridine (1.14 g, 4.33 mmol, 83% yield) as a light-yellow solid. |
Tags: 79491-46-6 synthesis path| 79491-46-6 SDS| 79491-46-6 COA| 79491-46-6 purity| 79491-46-6 application| 79491-46-6 NMR| 79491-46-6 COA| 79491-46-6 structure
A208768 [84487-15-0]
2-Bromo-5-nitropyridin-4-amine
Similarity: 0.61
A143548 [75711-00-1]
2-Chloro-3-methoxy-5-nitropyridine
Similarity: 0.62
A367994 [31872-76-1]
3-Bromo-4-methoxy-5-nitropyridine
Similarity: 0.60
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