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Chemical Structure| 182924-36-3 Chemical Structure| 182924-36-3

Structure of 182924-36-3

Chemical Structure| 182924-36-3

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Product Details of [ 182924-36-3 ]

CAS No. :182924-36-3
Formula : C6H5BrClN
M.W : 206.47
SMILES Code : BrCC1=CN=C(C=C1)Cl
MDL No. :MFCD07368893
InChI Key :YJOULMMJZAADRY-UHFFFAOYSA-N
Pubchem ID :6424661

Safety of [ 182924-36-3 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P280-P305+P351+P338-P310
Class:8
UN#:1759
Packing Group:

Computational Chemistry of [ 182924-36-3 ] 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 1.0
Num. H-bond donors 0.0
Molar Refractivity 42.08
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.

1.97
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

2.37
Log Po/w (WLOGP)?

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

2.48
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

3.01
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.

-3.04
Solubility 0.188 mg/ml ; 0.000911 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.

-2.28
Solubility 1.08 mg/ml ; 0.00523 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

-3.9
Solubility 0.0258 mg/ml ; 0.000125 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.

-5.88 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)

1.98

Application In Synthesis of [ 182924-36-3 ]

* 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 [ 182924-36-3 ]

[ 182924-36-3 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 16874-34-3 ]
  • [ 182924-36-3 ]
  • [ 919361-16-3 ]
  • 2
  • [ 21543-49-7 ]
  • [ 182924-36-3 ]
YieldReaction ConditionsOperation in experiment
85% With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 0 - 20℃; for 4.75h;Inert atmosphere; Synthesis 265-(Bromomethyl)-2-chloropyridine (26).To a solution of (6-chloropyridin-3-yl)methanol (1 .005 g, 7.0 mmol, 1 eq) in dry DCM(20 ml.) CBr4 (99%, 2.885 g, 8.6 mmol, 1 .2 eq) was added. This solution was cooled to 0C and then Ph3P (2.297 g, 8.7 mmol, 1 .2 eq) was added. The reaction mixture was stirred at 0C for 15 minutes under nitrogen atmosphere and then it was allowed to warm to room temperature. After 4.5 hours the reaction mixture was treated with 20 ml. of water and extracted with DCM. The combined organic extracts were dried over anhydrous Na2S04, filtered and the solvent was removed in vacuo. The residue was purified by flash chromatography on silica gel (n-Hex/EtOAc 9: 1 ) to afford 1 .231 g of 26 as white solid (85%).0.33 (n-Hex/EtOAc 9:1 ). 1 H NMR (400 MHz, CDCI3) δ 8.40 (d, J = 2.5 Hz, 1 H), 7.70 J = 8.2, 2.6 Hz, 1 H), 7.33 (d, J = 8.3 Hz, 1 H), 4.44 (s, 2H); 13C NMR (100 MHz, CDCI3) 5 151.4, 149.6, 139.5, 132.8, 124.6, 28.5; ESI MS m/z: calcd. for C6H6BrCIN [/W+H]+ 205.9, found: 205.9, 207.9, 209.9.
76.65% With phosphorus tribromide; In dichloromethane; at 0 - 20℃; for 3h; To a stirred solution of (6-chloropyridin-3-yl)methanol (2 g, 13.93 mmol) in dry DCM (40 ml), PBr3 (1.6 ml, 16.71 mmol) was added dropwise at 0C. The reaction mixture was stirred at ambient temperature for 3h. The progress of the reaction was monitored by TLC (3:7, Ethyl acetate: pet. ether). After completion of the reaction the reactionmixture was cooled o room temperature and quenched with aqueous 10% NaHCO3 solution (30 ml) and extracted with DCM (3 X 50 ml). The combined organic layer was dried over anhydrous sodium sulfate and removed under reduced pressure. The crude was purified by column chromatography (60-120 mesh silica gel) using 8% Ethyl acetate in pet ether as eluent to yield pure 5-(bromomethyl)-2-chloropyridine (2.2 g,76.65%) as a yellow oil.
62% With carbon tetrabromide; 1,3-bis-(diphenylphosphino)propane; In dichloromethane; (6-chloro-3-pyridinyl)-methanol (1.0 eq.) was taken up in dichloromethane and stirred overnight with carbon tetrabromide (1.5 eq.) and 1,3-bis(diphenylphosphino)propane (0.75 eq.) Ether was added to the solution and filtration followed by concentration of the filtrate afforded (6-chloro-3-bromomethyl) pyridine in 62% yield.
62% With carbon tetrabromide; 1,3-bis-(diphenylphosphino)propane; In dichloromethane; (6-Chloro-3-pyridinyl)-methanol (1.0 eq.) was taken up in dichloromethane and stirred overnight with carbon tetrabromide (1.5 eq.) and 1,3-bis(diphenylphosphino)propane (0.75 eq.). Ether was added to the solution and filtration followed by concentration of the filtrate afforded (6-chloro-3-bromomethyl)pyridine in 62% yield.
60% With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 0 - 20℃; for 16h; To a solution of 19-3B (115 mg, 0.804 mmol) in DCM (3 mL) was added carbon tetrabromide (320 mg, 0.965 mmol), triphenylphosphine (210 mg, 0.965 mmol), and stirred at 0 C to RT for 16 hr. The reaction mixture was diluted with excess DCM (20 mL), washed with water (20 mL), brine (10 mL) and dried over Na2S04, and the organic phase was concentrated under reduced pressure. Obtained crude compound was purified using silica gel chromatography (8% EtOAc in hexanes) to afford 19- 4B (100 mg, 0.48 mmol, yield 60%). MS (ESI): m/z 206.0 (M-l)+.
0.49 g With phosphorus tribromide; In dichloromethane; at 0 - 30℃; for 1.5h;Inert atmosphere; To a solution of 2-chloro-5-hydroxymethylpyridine (0.45 g, 0.003 mole) in DCM (10 mL) at 0 C under N2, was added phosphorus tribromide (0.44 mL, 0.0037 mole) drop wise. Reaction mixture was warmed to RT and stirred for 1.5 hours. The reaction mixture was diluted with DCM (75 mL), treated with saturated aqueous sodium bicarbonate (20 mL). Organic layer was washed with water (20 mL), brine solution (20 mL) and dried over Na2S04 and concentrated under vacuum to obtain the title compound. Yield: 0.49 g; lH - NMR (CDC13, 400 MHz) δ ppm: 4.35 (s, 2H), 7.32 - 7.34 (d, J = 8.2 Hz, 1H), 7.69 - 7.71 (dd, J = 2.2, 7.9 Hz, 1H), 8.40 - 8.41 (d, J = 1.7 Hz, 1H); Mass (m/z): 205.9, 208.0 (M+H)+.

 

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