Structure of 6635-90-1
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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. : | 6635-90-1 |
Formula : | C7H8N2O3 |
M.W : | 168.15 |
SMILES Code : | C1=C(OC)N=CC(=C1C)[N+]([O-])=O |
MDL No. : | MFCD03095075 |
InChI Key : | DJNQRLCFAHKFLZ-UHFFFAOYSA-N |
Pubchem ID : | 243169 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H317-H319 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.29 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 44.52 |
TPSA ? Topological Polar Surface Area: Calculated from |
67.94 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.56 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.35 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.31 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.21 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.37 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.73 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.97 |
Solubility | 1.8 mg/ml ; 0.0107 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.38 |
Solubility | 0.703 mg/ml ; 0.00418 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.91 |
Solubility | 2.05 mg/ml ; 0.0122 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) |
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 |
-6.37 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) |
1.98 |
* 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 |
---|---|---|
With hydrogen;palladium on activated charcoal; In tetrahydrofuran; at 20℃; for 6h; | Reference Example 50 6-Methoxy-4-methylpyridin-3-amine A mixture of 2-methoxy-4-methyl-5-nitropyridine4-Methyl-5-nitro-2-pyrrolidin-1-ylpyridine (1.68 g, 10.0 mmol) and 10% palladium on carbon (168 mg) in tetrahydrofuran (10 mL) was stirred under hydrogen atmosphere at room temperature for 6 hr. Catalyst was removed by filtration and the filtrate was concentrated in vacuo to give the title compound (1.31 g, 9.49 mmol, 95%) as a pale brown solid. 1H NMR (CDCl3) delta 2.16 (s, 3H), 3.28 (brs, 2H), 3.85 (s, 3H), 6.50 (s, 1H), 7.59 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In acetic acid; | b 5-Amino-2-methoxy-4-methylpyridine A mixture of stannous chloride dihydrate (41 g) and concentrated hydrochloric acid (40 ml) was added slowly to a solution of 2-methoxy-4-methyl-5-nitropyridine (5.1 g) in acetic acid (40 ml), maintaining the temperature below 35 C. The resulting mixture was stirred at room temperature for 2 hours, and then allowed to stand overnight in the refrigerator. The solid was collected and both solid and supernatant were separately basified with a 20% sodium hydroxide solution. The product was extracted with chloroform, combined, dried (anhydrous magnesium sulfate) and concentrated to give 3.9 g of the title compound as a solid, suitable for use in the next reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N,N-dimethyl-formamide dimethyl acetal;palladium; In ethanol; ethyl acetate; | A solution of 2-methoxy-4-methyl-5-nitropyridine (4.30 g, 25.57 mmol) and dimethylformamide dimethylacetal (35 ml) was heated at reflux under nitrogen for 40 hours. Ethyl acetate was added to this solution (150 ml), and this mixture was washed with water (150 ml). The aqueous extract was back-extracted with ethyl acetate (100 ml), and the organic extracts were combined, dried (Na2 O4), and evaporated under reduced pressure to yield a purple solid. The solid was dissolved in absolute ethanol (200 ml), and 5% palladium on carbon (3.0 g) was added to this solution which was shaken under a hydrogen atmosphere (3 atm) for 3 hours. The resultant reaction mixture was filtered, and the filtrate was evaporated under reduced pressure. Flash chromatography of the residue yielded compound 9 (2.05 g, 13.84 mmol, 54% last step, 50% overall) as a white crystalline solid: mp, 123-124 C.; IR (KBr) 1625, 1580, 1490, 1460, 1320, 1150 cm-1; 1 H NMR (DMSO-d6) delta 11.28 (br s, 1H), 8.37 (s, 1H), 7.57 (t, J=2.8 Hz, 1H), 6.86 (s, 1H), 6.33 (br m, 1H), 3.82 (s, 3H); 13 C NMR (DMSO-d6) delta 157.2, 136.4, 131.5, 130.7, 130.0, 99.6, 96.8, 53.4; LRMS (m/z, relative intensity) 149 (20), 148 (M+, 98), 147 (100), 119 (46), 118 (79), 117 (26), 105 (31), 91 (15), 70 (16); HRMS calculated for C8 H8 N2 O:148.0657, found: 148.0613. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; at 130℃; | 1. The mixture of 2-methoxy-4-methyl-5-nitropyridine (1.68g, 10.0 mmol) and 1,1- dimethoxy-N,N-dimethylmethanamine (14 Ml, 103 mmol) in 10 mL of DMF was heated at 130C overnight, cooled to RT, diluted with EtOAc, washed with water and brine, dried (MgS04), and concentrated. The residue was dissolved in 70 mL of EtOH. To this solution was added 1.06 g of 10% Pd/C. The mixture was stirred under 1 atm of hydrogen atmosphere over 4 days, filtered through a pad of Celite, and washed with EtOH. The filtrate was concentrated to give crude 5-methoxy-lH-pyrrolo[2,3-c]pyridine (quant). H NMR (399 MHz, DMSO-d6) delta ppm 11.26 (1 H, br. s.), 8.33 (1 H, s), 7.53 (1 H, d, 7=2.7 Hz), 6.73 - 6.88 (1 H, m), 6.32 (1 H, d, 7=3.1 Hz), 3.30 (3 H, s). |
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