Structure of 54915-41-2
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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. : | 54915-41-2 |
Formula : | C8H9NO3 |
M.W : | 167.16 |
SMILES Code : | OCC1=C([N+]([O-])=O)C=CC=C1C |
MDL No. : | MFCD12031847 |
InChI Key : | LIUYFMADDYMHLM-UHFFFAOYSA-N |
Pubchem ID : | 12204069 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 46.36 |
TPSA ? Topological Polar Surface Area: Calculated from |
66.05 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.35 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.58 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.24 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.68 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.03 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.96 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.11 |
Solubility | 1.3 mg/ml ; 0.00777 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.58 |
Solubility | 0.442 mg/ml ; 0.00264 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.99 |
Solubility | 1.72 mg/ml ; 0.0103 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 |
-6.2 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) |
1.78 |
* 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 |
---|---|---|
84% | With hydrogenchloride; In tetrahydrofuran; | EXAMPLE 28 Preparation of 2-methyl-6-nitrobenzyl alcohol. To a 0 solution of 54.30 g (0.30 moles) of <strong>[13506-76-8]2-methyl-6-nitrobenzoic acid</strong> in 500 ml of anhydrous tetrahydrofuran was added dropwise under a nitrogen atmosphere, 380 ml (0.38 moles) of a stock IM boran/THF solution at such a rate that the temperature did not exceed 5. Upon complete addition, the ice bath was removed, the solution allowed to stir at room temperature for 14 hours, heated to reflux for 4 hrs. and then cooled to 0 in an ice bath. The reaction was quenched by the dropwise addition of 400 ml of 10% hydrochloric acid, the solution heated to reflux on a steam bath for 0.5 hrs., the THF solvent distilled at atmospheric pressure and the insoluble precipitate extracted into methylene chloride. The methylene chloride extracts were combined, washed with satd. sodium bicarbonate solution, dried (Na2 SO4) and the solvent removed in vacuo affording a reddish colored semi solid. Purification was effected from 300 ml of carbon tetrachloride resulting in 41.35 g (84% yield) of yellow flakes; mp 67-8. Anal. calc'd. for C8 H9 NO3: C, 57.48; H, 5.43; N, 8.38. Found: C, 57.34; H, 5.42; N, 8.47. |
With hydrogenchloride; In tetrahydrofuran; | EXAMPLE 28 Preparation of 2-methyl-6-nitrobenzyl alcohol. To a 0 solution of 54.30 g (0.30 moles) of <strong>[13506-76-8]2-methyl-6-nitrobenzoic acid</strong> in 500 ml of anhydrous tetrahydrofuran was added dropwise under a nitrogen atmosphere, 380 ml (0.38 moles) of a stock IM boran/THF solution at such a rate that the temperature did not exceed 5. Upon complete addition, the ice bath was removed, the solution allowed to stir at room temperature for 14 hours, heated to reflux for 4 hrs. and then cooled to 0 in an ice bath. The reaction was quenched by the dropwise addition of 400 ml of 10% hydrochloric acid, the solution heated to reflux on a steam bath for 0.5 hrs., the THF solvent distilled at atmospheric pressure and the insoluble precipitate extracted into methylene chloride. The methylene chloride extracts were combined, washed with satd. sodium bicarbonate solution, dried (Na2 SO4) and the solvent removed in vacuo affording a reddish colored semi solid. Purification was effected from 300 ml of carbon tetrachloride resulting in 41.35 g (84% yield) of yellow flakes; mp 67-8. Anal. calc'd. for C8 H9 NO3: C, 57.48; H, 5.43; N, 8.38. Found: C, 57.34; H, 5.42; N, 8.47. | |
30.5 g | Reference Production Example 150 (0903) To a mixture of 15.6 g of sodium tetrahydroborate and 200 ml of tetrahydrofuran, 50 g of <strong>[13506-76-8]2-methyl-6-nitrobenzoic acid</strong> was added at room temperature. To the reaction mixture, 34 ml of dimethylsulfuric acid was added at 0C, followed by stirring at room temperature for 20 hours. 5% Hydrochloric acid (300 ml) was added at 0C, followed by stirring for one hour. After extraction with ethyl acetate, the organic layer was washed with water, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain 30.5 g of 2-methyl-6-nitrobenzyl alcohol (C150A). 1H-NMR (CDCl3) δ (ppm): 7.71 (1H, d, J = 7.7 Hz), 7.49 (1H, d, J = 7.5 Hz), 7.36 (1H, t, J= 7.9 Hz), 4.71 (2H, d, J = 7.2 Hz), 2.62 (1H, t, J = 7.4 Hz), 2.56 (3H, s). |
30.5 g | Reference Production Example 84 (1485) At room temperature, 50 g of <strong>[13506-76-8]2-methyl-6-nitrobenzoic acid</strong> was added to a mixture of 15.6 g of sodium borohydride and 200 ml of tetrahydrofuran. At 0 C., 34 ml of dimethylsulfuric acid was added to the reaction mixture, followed by stirring at room temperature for 20 hours. At 0 C., 300 ml of an aqueous 5% hydrochloric acid solution was added, followed by stirring for 1 hour. After extraction with ethyl acetate, the organic layer was washed with water, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain 30.5 g of 2-methyl-6-nitrobenzyl alcohol. (1486) 1H-NMR (CDCl3) δ (ppm): 7.71 (1H, d, J=7.7 Hz), 7.49 (1H, d, J=7.5 Hz), 7.36 (1H, t, J=7.9 Hz), 4.71 (2H, d, J=7.2 Hz), 2.62 (1H, t, J=7.4 Hz), 2.56 (3H, s). | |
To a solution of <strong>[13506-76-8]2-methyl-6-nitrobenzoic acid</strong> (2.0 g, 12.0 mmol)) in dichloromethane (20 ml) was added oxalyl (0684) chloride (3.47 g, 30.0 mmol) dropwise at 0C followed by (0685) addition of dimethylformamide (0.2 mL) . The reaction mixture was stirred at room temperature for lh. The reaction mixture was evaporated to dryness under reduced pressure. Dry THF was added to it make a clear solution followed by addition of sodium borohydride (1.2 g, 36.0 mmol) at 0C. The reaction mixture was stirred at room temperature for lh. It was (0686) quenched with water and extracted with ethyl acetate (3 x 50 mL) , washed with NH4C1 solution (3 x 30 mM) , dried over sodium sulfate and evaporated to dryness under reduced pressure to afford 2-methyl-6-nitrophenyl ) methanol as an off-white solid (1.65 g, crude) . It was used as such in the next step without any further purification. (0687) 1ti NMR (CDCI3) : δ 7.69 (d, J = 8.0 Hz 1H) , 7.45 (d, J = 7.60 Hz 1H 1H) , 7.34 (t, J = 8.0 Hz, 1H) , 4.69 (d, J = 7.2 Hz, 2H) , 2.64 (t, J = 7.6 Hz 1H) , 2.55 (s, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With hydrogenchloride; In tetrahydrofuran; | EXAMPLE 10 Synthesis of 2-methyl-6-nitrobenzyl alcohol A 100 mL round bottomed flask under dry argon was charged with 5 g of <strong>[13506-76-8]2-methyl-6-nitrobenzoic acid</strong> which was dissolved in 60 mL of dry tetrahydrofuran. To this solution was added slowly with cooling and stirring, 64.17 mL of a 1M solution of BH3.THF in THF. The mixture was refluxed for 17 h then the reaction was slowly and carefully quenched with an excess of 10% aqueous hydrochloric acid. The THF was removed under vacuum and the residue was extracted with three 50 mL aliquots of methylene chloride. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and the solvent removed. The crude product was recrystallized from methylene chloride/pentane to give 4.95 g of yellowish crystals (97% yield). |
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