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Chemical Structure| 54915-41-2

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Product Details of [ 54915-41-2 ]

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

Safety of [ 54915-41-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 54915-41-2 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

66.05 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.35
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.58
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.24
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

0.68
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.03
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.96

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.11
Solubility 1.3 mg/ml ; 0.00777 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.58
Solubility 0.442 mg/ml ; 0.00264 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-1.99
Solubility 1.72 mg/ml ; 0.0103 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.2 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

2.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.78

Application In Synthesis of [ 54915-41-2 ]

* 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.

  • Downstream synthetic route of [ 54915-41-2 ]

[ 54915-41-2 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 13506-76-8 ]
  • [ 54915-41-2 ]
YieldReaction ConditionsOperation 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)

  • 2
  • BH3.THF [ No CAS ]
  • [ 13506-76-8 ]
  • [ 54915-41-2 ]
YieldReaction ConditionsOperation 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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