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Chemical Structure| 308846-06-2 Chemical Structure| 308846-06-2

Structure of 308846-06-2

Chemical Structure| 308846-06-2

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Product Details of [ 308846-06-2 ]

CAS No. :308846-06-2
Formula : C7H5BrN2
M.W : 197.03
SMILES Code : BrCC1=CC=C(N=C1)C#N
MDL No. :MFCD09037857
InChI Key :VEPVNICICSNYPW-UHFFFAOYSA-N
Pubchem ID :21927727

Safety of [ 308846-06-2 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302+H312-H314
Precautionary Statements:P260-P264-P270-P280-P301+P312+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P362+P364-P405-P501
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 308846-06-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 41.79
TPSA ?

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

36.68 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.68
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

1.46
Log Po/w (WLOGP)?

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

1.7
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.

0.62
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

2.31
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.55

Water Solubility

Log S (ESOL):?

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

-2.36
Solubility 0.861 mg/ml ; 0.00437 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.

-1.84
Solubility 2.87 mg/ml ; 0.0146 mol/l
Class?

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

Very 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

-3.37
Solubility 0.0837 mg/ml ; 0.000425 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.

-6.47 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

1.0 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)

2.19

Application In Synthesis of [ 308846-06-2 ]

* 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.

  • Upstream synthesis route of [ 308846-06-2 ]

[ 308846-06-2 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 1620-77-5 ]
  • [ 308846-06-2 ]
YieldReaction ConditionsOperation in experiment
53% With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In chloroform at 60℃; for 6 h; Commercially available 2-cyano-5-methylpyridine (1.90 g, 16.1 mmol) was dissolved in chloroform (100 mL), and the mixture was stirred at 60°C for 6 hours after adding N-bromosuccinimide (4.29 g, 24.1 mmol) and α,α-azobisisobutyronitrile (0.792 g, 4.82 mmol). After ice-cooling the reaction mixture, the precipitate was separated by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give 5-bromomethyl-2-cyanopyridine (1.69 g, 53percent). 1H NMR (CDCl3) δ(ppm) 4.80 (s, 2H), 8.03 (dd, J = 0.92, 8.07 Hz, 1H), 8.12 (dd, J = 2.20, 8.07 Hz, 1H), 8.81 (bd, J = 1.83 Hz, 1H).
44% With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In tetrachloromethane for 4 h; Heating / reflux Preparation 16; 2-Aminomethyl-5-o-propylthiomethyl-pyridine; 5-Bromomethyl-pyridine-2-carbonitrile; Add AIBN (0.25 g, 1.5 mmol) to a slurry of 5- methyl-pyridine-2-carbonitrile (2.5 g, 21.1 mmol) and NBS (3.7 g, 21.1 mmol) in carbon tetrachloride (150 mL) at reflux under a nitrogen atmosphere. Add AIBN (3x0.25 g, 3x1.5 mmol) to the reaction in 0.25 g portions every hour for 3 h. Stir the resulting mixture for one additional hour at reflux. Cool the mixture to room temperature and wash with saturated aqueous NaHCO3 (30 mL). Collect the organic phase, concentrate in EPO <DP n="72"/>vacuo and purify the residue by chromatography on silica gel (330 g) eluting with DCM to obtain the desired intermediate (1.8 g, 44percent). MS (ES+) m/z: 199 (M+2)+.
References: [1] Patent: EP2163554, 2010, A1, . Location in patent: Page/Page column 52-53.
[2] Patent: WO2007/28083, 2007, A2, . Location in patent: Page/Page column 69-70.
[3] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 7, p. 1017 - 1022.
[4] Journal of Medicinal Chemistry, 2003, vol. 46, # 17, p. 3612 - 3622.
[5] Patent: WO2011/20615, 2011, A1, . Location in patent: Page/Page column 57; 58.
[6] Patent: EP2289883, 2011, A1, . Location in patent: Page/Page column 26.
[7] Patent: WO2012/128582, 2012, A2, . Location in patent: Page/Page column 42.
[8] Organic Letters, 2017, vol. 19, # 14, p. 3895 - 3898.
  • 2
  • [ 1620-77-5 ]
  • [ 94-36-0 ]
  • [ 308846-06-2 ]
YieldReaction ConditionsOperation in experiment
51% With N-Bromosuccinimide In tetrachloromethane B)
6-Cyano-3-picolylbromide
A mixture of 6-cyano-3-picoline (1.32 g, 11.19 mmol), benzoylperoxide (0.54 g, 2.24 mmol), and N-bromosuccinimide (2.8 g, 15.7 mmol) in carbontetrachloride (30 mL) was heated at reflux for 2 h.
The resulting suspension was filtered and the filtrate diluted with dichloromethane (400 mL), washed with a saturated sodium bicarbonate solution, dried over magnesium sulfate, and concentrated in vacuo.
The residue was purified by column chromatography (EtOAc: n-hexane, 1:9) to give the title compound as a yellow oil (1.12 g, 51percent).
1H NMR (CDCl3) δ8.64 (s, 1H), 7.76 (d, 1H), 7.63 (d, 1H), 4.55 (s, 2H).
FAB MS: 197 [M+1]+
References: [1] Patent: US2002/169113, 2002, A1, .
  • 3
  • [ 3510-66-5 ]
  • [ 308846-06-2 ]
References: [1] Journal of Medicinal Chemistry, 2003, vol. 46, # 17, p. 3612 - 3622.
[2] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 7, p. 1017 - 1022.
[3] Patent: WO2011/20615, 2011, A1, .
[4] Patent: EP2289883, 2011, A1, .
[5] Patent: WO2012/128582, 2012, A2, .
 

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