Structure of 20265-35-4
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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.
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CAS No. : | 20265-35-4 |
Formula : | C6H6N2O3 |
M.W : | 154.12 |
SMILES Code : | O=[N+](C1=CC=CN=C1OC)[O-] |
MDL No. : | MFCD00023459 |
InChI Key : | WZNQCVOSOCGWJG-UHFFFAOYSA-N |
Pubchem ID : | 253219 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 11 |
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 | 39.55 |
TPSA ? Topological Polar Surface Area: Calculated from |
67.94 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.14 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.99 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.8 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.52 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.69 |
Solubility | 3.14 mg/ml ; 0.0204 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.01 |
Solubility | 1.52 mg/ml ; 0.00988 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.52 |
Solubility | 4.68 mg/ml ; 0.0303 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 |
No |
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) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
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 |
-6.54 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 |
1.0 |
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 |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.97 |
* 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 |
---|---|---|
90% | In methanol; at 0℃; for 4h; | A suspension of sodium methoxide (40.5 g, 0.750 mol) in 200 mL of methanol was slowly added to a solution of 2-chloro-3- nitro-pyridine (79.3 g, 0.500 mol) in 800 mL of methanol at 0 °C. The reaction mixture was stirred for 4 hours and then poured into 1000 g of ice. The resulting precipitate was filtered, washed with water, and dried to give 2-methoxy-3-nitro-pyridine (70. g, 0.45 mmol, 90 percent) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With hydrogen;palladium 10% on activated carbon; In methanol; for 4h; | (1)10percent palladium-activated carbon (2.5 g) was added to a solution of commercially available <strong>[20265-35-4]2-methoxy-3-nitropyridine</strong> (50.5 g) in methanol (500 mL), and the mixture was stirred for four hours in a hydrogen atmosphere.The reaction solution was filtered through celite, and then the filtrate was concentrated under reduced pressure.The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1) to give 2-methoxypyridin-3-amine as a yellow powder (37.2 g, 92percent).1H NMR (300 MHz, CDCl3) delta ppm 3.64-3.88 (m, 2H), 3.92-4.05 (m, 3H), 6.67-6.76 (m, 1H), 6.84-6.92 (m, 1H), 7.54-7.62 (m, 1H).MS(+): 125 [M+H]+. |
90% | palladium-carbon; In ethanol; | EXAMPLE 13 Synthesis of 2-methoxy-3-aminopyridine STR28 To a solution of the compound of Example 12 (17.12 g, 0.11 mol) in ethanol (180 mL) in a Parr bottle, was added 4percent Pd/C (3.43 g). The bottle was sealed, purged with nitrogen and was pressurized (5 psi) with hydrogen. After stirring at room temperature for 2 hr, the reaction vessel was vented, purged with nitrogen and filtered. The clear filtrate was concentrated to give the title compound (15.3 g, 90percent). 1 H NMR (CDCl3): 7.58 (dd, J=5, 2 Hz, 1H); 6.87 (dd, J=8, 2 Hz, 1H); 6.72 (dd, J=8, 5 Hz, 1H); 3.98 (s, 3H). |
87% | With hydrogen;palladium 10% on activated carbon; In methanol; for 15h; | A solution of 2- methoxy-3-nitro-pyridine (70. g, 0.45 mol) in methanol (700 mL) containing palladium on carbon (7 g, 10 percent) was stirred under an atmosphere of hydrogen for 15 hours. The catalyst was filtered and washed with methanol. The filtrate was evaporated to dryness to give crude 2- methoxy-pyridin-3-ylamine (48 g, 0.39 mol, 87 percent), which was used directly in the next step. |
74% | With hydrogen;palladium 10% on activated carbon; In methanol; | Compound 1 (20.8 g, 135 mmol) was dissolved in methanol (270 mL) and palladium on carbon (10percent Pd dry weight basis, Degussa type E101 NE/W, 50percent water content, 5.75 g, 2.7 mmol Pd) was added. The atmosphere was replaced with hydrogen (toggle between vacuum and hydrogen from a balloon five times), the mixture was stirred overnight, then filtered. The filtrate was concentrated under vacuum and the residue was taken up in a 1:1 hexanes:ethyl acetate mixture and washed with a 4:1 mixture of water and saturated NaHCO3, saturated NaHCO3 and brine. The organic layer was dried over MgSO4 and filtered and the filtrate was concentrated under reduced pressure to give compound 2 (12.43 g, 74percent) as a white solid. This material was used without purification. |
38.9 g | With palladium 10% on activated carbon; hydrogen; In methanol; for 3h; | A solution of <strong>[20265-35-4]2-methoxy-3-nitropyridine</strong> (50 g, 324.4 mmol) and 10percent Pd/C (5 g) in MeOH (500 ml_) was stirred under an atmosphere of H2 for 3 h. The mixture was filtered through celite and the filter was washed with MeOH. The filtrate was concentrated in vacuo to yield 2-methoxypyridin-3-amine as a brown solid (38.9 g, 313.4 mmol). 1H NMR: (300 MHz, CDCI3) delta: 3.74 (br. s, 2H), 3.96 (s, 3H), 6.72 (m, 1 H), 6.86 (m, 1 H), 7.56 (d, J=1.8, 1 H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21.27% | In tetrahydrofuran; at -78 - -20℃; | To a mixture of 2-methoxy-3- nitropyridine (5 g, 0.032 mol) in tetrahydrofuran (100 mL) at -78°C was added dropwise vinylmagnesium bromide (100 mL, 1 M). The reaction mixture was stirred at -20°C overnight then quenched with saturated aqueous NH4CI and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous Na2SC>4, and concentrated under reduced pressure. The residue was purified by flash column chromatography to afford the desired product (1 g, 21.27percent yield) as black solid. LC-MS: 149 (M+H)+. |
100 mg | In tetrahydrofuran; methanol; at -78 - -20℃; for 6h; | Method 4 Synthesis of 7-methoxy-1H-pyrrolo[2,3-c]pyridine (Intermediate 5) A solution of R-4 (500 mg, 3.24 mmol) in anhydrous THF (20 mL) is cooled to -78° C. and vinylmagnesium bromide (9.73 mL of a 1 M solution in THF, 9.73 mmol) added. The reaction is stirred at -20° C. for 6 h then quenched with saturated aqueous NH4Cl solution and extracted with EtOAc. The organic phase is concentrated in vacuo and the crude material purified by flash chromatography (SiO2, 2percent to 10percent MeOH in DCM) to give the title intermediate I-5 (100 mg) m/z 148.9 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With sodium methylate; In methanol; | EXAMPLE 12 Synthesis of 2-methoxy-3-nitropyridine STR27 2-Chloro-3-nitropyridine (25 g, 0.157 mol) was suspended in methanol (300 ml) and sodium methoxide (17 g, 0.315 mol) was added. The mixture was refluxed for 2 hr and part of the solvent removed under reduced pressure. The reaction mixture was diluted with water (1 litre) and the precipitate collected by filtration. The white solid obtained was washed with more water and dried under vacuum to give the title compound (18.2 g, 75percent). 1 H NMR (CDCl3): 8.42 (dd, J=5, 2 Hz, 1H); 8.28 (dd, J=8, 2 Hz, 1H); 7.06 (dd, J=8, 5 Hz, 1H); 4.13 (s, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium acetate; In water; | EXAMPLE 5 Preparation of 3-Nitro-2-aminopyridine One gram (6.5 mmol) of <strong>[20265-35-4]2-methoxy-3-nitropyridine</strong> and 5.0 g (65 mmol) of ammonium acetate were added to a 100 ml round bottom flask. The reaction mixture was heated at 150° C. for approximately 16 hours under an argon atmosphere. An additional 5 g of ammonium acetate was added to the reaction mixture which was allowed to heat for an additional 8 hours. Thin layer chromatography of the mixture indicated that both product and starting material were present. The reaction mixture was cooled and poured into approximately 100 ml of water. The precipitated solid was collected by filtration to provide 209.8 mg of 3-nitro-2-aminopyridine. m/e 139. The NMR spectrum of the collected produot was identical to that of an authentic reference standard. Analysis calculated for C5 H5 N3 O2: Theory: C, 43.17; H, 3.62; N, 30.21; Found: C, 42.89; H, 3.38; N, 30.23. |
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