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Structure of 131747-45-0

Chemical Structure| 131747-45-0

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Product Details of [ 131747-45-0 ]

CAS No. :131747-45-0
Formula : C6H6BrNO
M.W : 188.02
SMILES Code : OCC1=NC=CC(Br)=C1
MDL No. :MFCD09800557
Boiling Point : No data available
InChI Key :MHVUUSQGWMQSMH-UHFFFAOYSA-N
Pubchem ID :14761462

Safety of [ 131747-45-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 131747-45-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 38.06
TPSA ?

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

33.12 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

0.69
Log Po/w (WLOGP)?

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

1.18
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.

0.65
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

1.89
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.22

Water Solubility

Log S (ESOL):?

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

-1.87
Solubility 2.55 mg/ml ; 0.0136 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-0.96
Solubility 20.5 mg/ml ; 0.109 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

-2.71
Solubility 0.368 mg/ml ; 0.00196 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

No
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.

-6.96 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

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)

1.53

Application In Synthesis of [ 131747-45-0 ]

* 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 [ 131747-45-0 ]

[ 131747-45-0 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 131747-45-0 ]
  • [ 131747-63-2 ]
YieldReaction ConditionsOperation in experiment
100% With manganese(IV) oxide; In chloroform; for 0.75h;Reflux; Example 29i 4-Bromopicolinaldehyde Manganese(IV) oxide (22.19 g, 255.29 mmol) was added to a solution of (4-bromopyridin-2-yl)methanol (4.00 g, 21.27 mmol) in chloroform (80 mL) and the reaction mixture was stirred under reflux for 45 min. After the mixture had cooled to room temperature the solids were removed by filtration through a pad of Celite.(R).. The solvent was removed in vacuo and the residue (3.96 g, quant.) was used without further purification in the next step. 1H NMR (500 MHz, DMSO-d6) delta ppm 9.97 (s, 1H) 8.80 (d, 1H) 7.98 (d, 1H) 7.88 (dd, 1 H); MS (APCI+): m/z 186, 188 [M+H]+.
75% With oxalyl dichloride; dimethyl sulfoxide; triethylamine; In dichloromethane; at -65 - -60℃; for 1.5h;Inert atmosphere; Under the protection of nitrogen,Add 3L DCM to the 5L three-neck bottle to cool down.240g of oxalyl chloride was added dropwise during cooling;At -60 ° C,295.6 g of Dimethyl sulfoxide (DMSO) was added dropwise to the reaction solution.Keep warm for 30min;At -60 ° C,237.5 g of Cpd 3 was added dropwise to the reaction solution.The reaction was carried out at -65 ° C for 1 hour;At this temperature, 3.5 eq of triethylamine (TEA) was added dropwise.After the solution was allowed to stand, the plate was measured.Through the column, the product 4-bromopyridine-2-carbaldehyde is obtained.(Cpd 4) 177.2g,The yield was 75percent.
Description 5: 4-Bromo-2-pyridinecarbaldehyde (D5); To a solution of the oxalyl chloride (0.364 mL, 4.09 mmol) in dry DCM (30 mL) at -780C was added DMSO (0.634 mL, 8.93 mmol) in dry DCM (5 mL) dropwise. The mixture was stirred at this temperature under argon atmosphere for 10 minutes <n="29"/>before a solution of (4-bromo-2-pyridinyl)methanol (D4) (700 mg, 3.72 mmol) in dry DCM (15 ml.) was added dropwise. After circa 30 minutes, triethylamine (2.6 mL, 18.6 mmol) was added and the cooling bath was removed. The reaction mixture was allowed to stir at room temperature for 1 h after which water was added and it was extracted 3 times with DCM. The combined organics were dried over MgSO4. The crude material (700 mg) was purified by flash chromatography (Biotage SP4, 25+M column) with a gradient of EtOAc in hexane to afford 425 mg (61 percent) of the desired product D5.1H-NMR (CDCI3): delta 7.70 (1 H, dd), 8.12 (1 H1 d), 8.61 (1 H, d), 10.05 (1 H, s); Description 5 - alternative procedure: 4-Bromo-2-pyridinecarbaldehyde (D5); To a solution of oxalyl chloride (13.2 mL, 0.149 mol) in dry dichloromethane (1 L) at - 78 0C under argon was added a solution of DMSO (23 mL, 0.324 mol) in dry dichloromethane (180 mL) dropwise over 20 minutes. The mixture was stirred at -78 0C under argon for 15 minutes and then a solution of (4-bromo-2-pyridinyl)methanol (D4) (25.4 g, 0.135 mol) in dry dichloromethane (500 mL) was added dropwise over 30 minutes. The resulting white suspension was stirred at -78 CC for 40-45 minutes and then triethylamine (95 mL, 0.676 mol) was added dropwise over 15 minutes. After stirring at -78 0C for 15 minutes, the mixture was allowed to reach room temperature over -1.5 h and then poured into water (400 mL). The organic layer was separated and the aqueous layer was extracted with dichloromethane (3x, ~1 L total solvent). The combined organic layers were washed with brine (20OmL), dried over MgSO4 and concentrated. The crude material was purified by flash chromatography on silica gel with a gradient of 0 to 30 percent ethyl acetate in hexane to afford 20.5 g (82percent) of the desired product D5, with NMR data consistent with those previously obtained.
  • 2
  • [ 13508-96-8 ]
  • [ 131747-45-0 ]
 

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