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Structure of 27063-92-9

Chemical Structure| 27063-92-9

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Product Details of [ 27063-92-9 ]

CAS No. :27063-92-9
Formula : C7H8BrN
M.W : 186.05
SMILES Code : CC1=CC(C)=NC=C1Br
MDL No. :MFCD09842454
InChI Key :SLMUXUHXAIPROA-UHFFFAOYSA-N
Pubchem ID :13411100

Safety of [ 27063-92-9 ]

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

Computational Chemistry of [ 27063-92-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.29
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 41.87
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

12.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.14
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

2.31
Log Po/w (WLOGP)?

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

2.46
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.

1.91
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

2.94
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.35

Water Solubility

Log S (ESOL):?

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

-2.94
Solubility 0.213 mg/ml ; 0.00114 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.

-2.22
Solubility 1.12 mg/ml ; 0.00604 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

-3.65
Solubility 0.0415 mg/ml ; 0.000223 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.

-5.79 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

2.0
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

0.0 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)

1.41

Application In Synthesis of [ 27063-92-9 ]

* 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 [ 27063-92-9 ]

[ 27063-92-9 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 108-47-4 ]
  • [ 27063-92-9 ]
  • [ 29976-20-3 ]
  • [ 27063-93-0 ]
YieldReaction ConditionsOperation in experiment
22%; 12%; 35% Bromination of 2,4-lutidineTo 2,4-lutidine (5.39 mL, 46.7 mmol, 1 eq.) was added oleum (50 mL, containing 20percent free SO3) carefully under stirring at 0 0C. The reaction flask was fitted with a high-efficiency reflux condenser and heated to 165 °C in an oil bath. Bromine (4.3O mL, 83.4 mmol, 0.9 eq.) was added in portions of 0.5 mL over 5 h, and stirring was continued at 155-175 °C for 20 h. The solution was cooled to room temperature, poured on crushed ice (200 g) and stirred for 1 h. The resulting orange solution was neutralised by careful addition of solid Na2CO3, diluted with water and extracted with EtOAc (2 x 250 mL). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The crude residue was purified by automated flash column chromatography (Biotage KP-Sil.(TM). SNAP 340 g cartridge, 0-15percent EtOAc/hexane) and dried in vacuo to furnish bromolutidines 8, 9 and 10.3,5-Dibromo-2,4-dimethylpyridine 8White solid (1.48 g, 12percent); mp 28-30 °C; 1H NMR deltaH (400 MHz; CDCl3) 2.54 (s, 3H, CH3), 2.61 (s, 3Eta, CH3), 8.41 (s, 1Eta, pyHortho); 13C NMR deltac (100 MHz; CDCl3) 23.8 (CH3), 25.7 (CH3), 120.3 (ArQ, 124.4 (ArQ, 146.4 (ArQ, 148.5 (ArCH), 156.5 (ArQ; IR vmax (filmVcm"1 3045, 2998, 2956, 2921, 1558, 1433, 1376, 1349, 1232, 1049, 993, 928, 783; HRMS (ESI+) for C7H8Br2N requires 263.9018, found (M+H+) 263.9027;5-Bromo-2,4-dimethylpyridine 9Colourless oil (1.89 g, 22percent); 1K NMR deltaH (400 MHz; CDCl3) 2.32 (s, 3H, CH3), 2.44 (s, 3Eta, CH3), 7.00 (s, 1Eta, pyHortho), 8.47 (s, 1Eta, pyHmeta); 13C NMR deltac (100 MHz; CDCl3) 22.1 (CH3), 23.6 (CH3), 120.4 (ArQ, 125.5 (ArCH), 146.7 (ArQ, 150.5 (ArCH), 157.0 (ArQ; IR vmax (filmycm"1 2985, 2957, 2924, 2854, 1592, 1461, 1377, 1353, 1289, 1177, 1032; HRMS (ESI+) for C7H9BrN requires 185.9913, found (M+H+) 185.9918;3-Bromo-2,4-dimethyIpyridine 10Colourless oil (3.04 g, 35percent); 1U NMR deltaH (400 MHz; CDCl3) 2.33 (s, 3H, CH3), 2.61 (s, 3Eta, CH3), 6.91 (d, J=5.0 Hz, IH, pyHmeta), 8.18 (d, J=5.0 Hz, IH, pyHortho); 13C NMR deltac (100 MHz; CDCl3) 23.2 (CH3), 25.7 (CH3), 123.4 (ArCH), 124.3 (ArQ, 146.7 (ArCH), 147.3 (ArQ, 157.4 (ArQ; IR vmax (filn^/cm-1 3050, 2995, 2958, 2922, 1585, 1437, 1389, 1123, 1024, 916, 825; HRMS (ESI+) for C7H9BrN requires 185.9913, found (M+H+) 185.9917;
  • 2
  • [ 108-47-4 ]
  • [ 27063-92-9 ]
  • [ 27063-93-0 ]
YieldReaction ConditionsOperation in experiment
With bromine; Example 1 Preparation of 5-bromo-2,4-dimethylpyridine STR13 150 ml of 65percent strength oleum are added dropwise to 28.9 ml of 2,4-dimethylpyridine, while cooling with ice and stirring, such that the temperature does not rise above 35° C. When the solution has become homogeneous, 6.42 ml of bromine are slowly added dropwise, with stirring. The mixture is stirred at 80° C. for 31/2 hours. After cooling, it is carefully added dropwise to 1 kg of ice, neutralized with solid Na2 CO3 and extracted 3 times with 300 ml of ether each time. The organic layer is separated off and dried over magnesium sulfate. After removal of the solvent by distillation in vacuo, 34.6 g of a pale yellow oil consisting of the isomers 5-bromo-2,4-dimethylpyridine and 3-bromo-2,4-dimethylpyridine are obtained.
  • 3
  • [ 27063-93-0 ]
  • [ 27063-92-9 ]
YieldReaction ConditionsOperation in experiment
The isomers are separated by column chromatography on silicon dioxide gel to give 10 g of 5-bromo-2,4-dimethylpyridine as a colorless liquid (13.0 g of <strong>[27063-93-0]3-bromo-2,4-dimethylpyridine</strong>). Yield: 22percent.
  • 4
  • [ 108-47-4 ]
  • iron(II) sulfate [ No CAS ]
  • [ 27063-92-9 ]
  • [ 27063-93-0 ]
YieldReaction ConditionsOperation in experiment
With bromine; (a) Oleum (65percent, 600 ml) was carefully added to cold 2,4-dimethylpyridine (107.4 g). Bromine (80 g) was added and the mixture was heated for 20 hours at 55°, allowed to cool and poured on to ice. The mixture was neutralised with aqueous sodium hydroxide and extracted with ether. The ether extracts were stirred with ferrous sulphate overnight, evaporated and the residue was distilled to give a mixture of 3-bromo-2,4-dimethylpyridine and 5-bromo-2,4-dimethylpyridine (66.6 g, b.p. 88°-90° at 11 mm Hg).
  • 5
  • [ 29976-20-3 ]
  • [ 27063-92-9 ]
  • [ 27063-93-0 ]
 

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