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Chemical Structure| 1196146-82-3 Chemical Structure| 1196146-82-3
Chemical Structure| 1196146-82-3

5-Bromo-2-chloro-4-hydroxypyridine

CAS No.: 1196146-82-3

4.5 *For Research Use Only !

Cat. No.: A553891 Purity: 95%

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Product Details of [ 1196146-82-3 ]

CAS No. :1196146-82-3
Formula : C5H3BrClNO
M.W : 208.44
SMILES Code : OC1=CC(Cl)=NC=C1Br
MDL No. :MFCD13189877
InChI Key :HKPSSVMYMKAABY-UHFFFAOYSA-N
Pubchem ID :72212503

Safety of [ 1196146-82-3 ]

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

Calculated chemistry of [ 1196146-82-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 38.97
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.

1.43
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

2.15
Log Po/w (WLOGP)?

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

2.2
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.

1.19
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

2.27
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.85

Water Solubility

Log S (ESOL):?

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

-2.98
Solubility 0.218 mg/ml ; 0.00105 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.

-2.48
Solubility 0.694 mg/ml ; 0.00333 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

-2.92
Solubility 0.248 mg/ml ; 0.00119 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.

-6.04 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

0.0
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)

1.78

Application In Synthesis [ 1196146-82-3 ]

* 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 [ 1196146-82-3 ]

[ 1196146-82-3 ] Synthesis Path-Downstream   1~21

  • 1
  • [ 1196146-82-3 ]
  • [ 1895-39-2 ]
  • 5-bromo-2-chloro-4-(difluoromethoxy)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2.0h; To solution of <strong>[1196146-82-3]5-bromo-2-chloro-pyridin-4-ol</strong> (800 mg, 3.84 mmol) in DMF (10 ml) were added sodium chlorodifluoroacetate (700 mg, 4.61 mmol) and Cs2CO3 (1.87 g, 5.76 mmol) and the RM was heated at 100 C. for 2 h. The RM was treated with ice cold water and was extracted with diethyl ether. The combined organic layers were washed with water, brine, were dried and the volatiles were removed under reduced pressure to get a crude compound which was purified by CC (SiO2, EtOAc/Hex) to afford the desired compound (600 mg, 60%).
With caesium carbonate; In N,N-dimethyl-formamide; at 110 - 115℃; A solution of <strong>[1196146-82-3]5-bromo-2-chloropyridin-4-ol</strong> (200 g 0.960 mol, Intermediate 56) and sodium chlorodifluoroacetate (264 g, 1.73 mol) in DMF (1 L) was added dropwise to a 110-115 C. suspension of Cs2CO3 (469 g, 1.44 mol) in DMF (1 L), and the resulting mixture was stirred at 110-115 C. After the reaction went to completion, mixture was allowed to cool to 50-60 C., and then it was poured into ice water. The resulting mixture was extracted twice with MTBE, and the combined organic layers were washed with water and then concentrated. The concentrate was purified by distillation to afford the title compound as a colorless liquid (bp 75-78 C. at 1-2 mmHg).
With caesium carbonate; In N,N-dimethyl-formamide; at 110 - 115℃; A solution of <strong>[1196146-82-3]5-bromo-2-chloropyridin-4-ol</strong> (200 g 0.960 mol, Intermediate 53) and sodium chlorodifluoroacetate (264 g, 1.73 mol) in DMF (1.0 L) was added dropwise to a 110-115 C. suspension of Cs2CO3 (469 g, 1.44 mol) in DMF (1.0 L), and the resulting mixture was stirred at 110-115 C. After the reaction went to completion, mixture was allowed to cool to 50-60 C., and then it was poured into ice water. The resulting mixture was extracted twice with MTBE, and the combined organic layers were washed with water and then concentrated. The concentrate was purified by distillation to afford the title compound as a colorless liquid (bp 75-78 C. at 1-2 mmHg).
  • 2
  • [ 1196146-82-3 ]
  • 5-[4-(difluoro-methoxy)-6-ethoxy-pyridin-3-yl]-N-(2,6-difluoro-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid amide [ No CAS ]
  • 3
  • [ 1196146-82-3 ]
  • C12H10ClF2N3O3 [ No CAS ]
  • 4
  • [ 1196146-82-3 ]
  • C14H15F2N3O4 [ No CAS ]
  • 5
  • [ 17368-12-6 ]
  • [ 1196146-82-3 ]
  • 6
  • 3,5-dibromo-2-chloropyridin-4-ol [ No CAS ]
  • [ 1196146-82-3 ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; In tetrahydrofuran; at -78℃; for 0.166667h; n-Butyl lithium (2.71 L, 2.5 M, 6.8 mol) was added dropwise to a stirring -78 C. solution of 3,5-dibromo-2-chloropyridin-4-ol (1130 g, 3.93 mol, Intermediate 55) in THF (13.6 L), and the resulting mixture was stirred at -78 C. for 10 min. After this time, water (2 L) was added dropwise to the reaction mixture, and then the mixture was allowed to warm to 0-5 C. The mixture was then washed three times with 2 N aqueous HCl, and the combined aqueous washes were back-extracted twice with EtOAc. All the organic layers were then combined and concentrated. The concentrate was stirred as a slurry in heptane at 25-30 C. for 3 h, filtered, and then dried under vacuum to afford the title compound as a light-yellow solid.
With n-butyllithium; In tetrahydrofuran; at -78℃; for 0.166667h; n-Butyllithium (2.71 L, 2.5 M, 6.8 mol) was added dropwise to a stirring -78 C. solution of 3,5-dibromo-2-chloropyridin-4-ol (1.13 kg, 3.93 mol, Intermediate 52) in THF (13.6 L), and the resulting mixture was stirred at -78 C. for 10 min. After this time, water (2 L) was added dropwise to the reaction mixture, and then it was allowed to warm to 0-5 C. The mixture was then washed three times with 2 N aqueous HCl, and the combined aqueous washes were back-extracted twice with EtOAc. All the organic layers were then combined and concentrated. The concentrate was slurried with heptane at 25-30 C., stirred for 3 h, filtered, and then dried under vacuum to afford the title compound as a light-yellow solid.
  • 7
  • [ 1196146-82-3 ]
  • 4-chloro-5-(4-(difluoromethoxy)-6-(3,3,3-trifluoro-2,2-dimethylpropyl)pyridin-3-yl)-1-ethyl-N-(((1r,4r)-4-sulfamoylcyclohexyl)methyl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 8
  • [ 1196146-82-3 ]
  • N-(((1r,4r)-4-(N-acetylsulfamoyl)cyclohexyl)methyl)-4-chloro-5-(4-(difluoromethoxy)-6-(3,3,3-trifluoro-2,2-dimethylpropyl)pyridin-3-yl)-1-ethyl-1H-pyrazole-3-carboxamide [ No CAS ]
  • 9
  • [ 1196146-82-3 ]
  • 4-chloro-5-(4-(difluoromethoxy)-6-(3,3,3-trifluoro-2,2-dimethylpropyl)pyridin-3-yl)-1-ethyl-N-(((1r,4r)-4-(N-(methylcarbamoyl)sulfamoyl)cyclohexyl)methyl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 10
  • [ 1196146-82-3 ]
  • N-(((1r,4r)-4-(N-carbamoylsulfamoyl)cyclohexyl)methyl)-4-chloro-5-(4-(difluoromethoxy)-6-(3,3,3-trifluoro-2,2-dimethylpropyl)pyridin-3-yl)-1-ethyl-1H-pyrazole-3-carboxamide [ No CAS ]
  • 11
  • [ 1196146-82-3 ]
  • ethyl 5-(6-chloro-4-(difluoromethoxy)pyridin-3-yl)-1-ethyl-1H-pyrazole-3-carboxylate [ No CAS ]
  • 12
  • [ 1196146-82-3 ]
  • ethyl 5-(4-(difluoromethoxy)-6-(3,3,3-trifluoro-2,2-dimethylpropyl)pyridin-3-yl)-1-ethyl-1H-pyrazole-3-carboxylate [ No CAS ]
  • 13
  • [ 1196146-82-3 ]
  • ethyl 4-chloro-5-(4-(difluoromethoxy)-6-(3,3,3-trifluoro-2,2-dimethylpropyl)pyridin-3-yl)-1-ethyl-1H-pyrazole-3-carboxylate [ No CAS ]
  • 14
  • [ 1196146-82-3 ]
  • ethyl 4-chloro-5-(6-chloro-4-(difluoromethoxy)pyridin-3-yl)-1-ethyl-1H-pyrazole-3-carboxylate [ No CAS ]
  • 15
  • [ 1196146-82-3 ]
  • ethyl (S*)-4-chloro-5-(4-(difluoromethoxy)-6-(3,3,3-trifluoro-2-methylpropyl)pyridin-3-yl)-1-ethyl-1H-pyrazole-3-carboxylate [ No CAS ]
  • 16
  • [ 1196146-82-3 ]
  • (S*)-4-chloro-5-(4-(difluoromethoxy)-6-(3,3,3-trifluoro-2-methylpropyl)pyridin-3-yl)-1-ethyl-1H-pyrazole-3-carboxylic acid [ No CAS ]
  • 17
  • [ 1196146-82-3 ]
  • ethyl 4-chloro-5-(4-(difluoromethoxy)-6-(4,4,4-trifluorobutyl)pyridin-3-yl)-1-ethyl-1H-pyrazole-3-carboxylate [ No CAS ]
  • 18
  • [ 1196146-82-3 ]
  • 4-chloro-5-(4-(difluoromethoxy)-6-(3,3,3-trifluoro-2,2-dimethylpropyl)pyridin-3-yl)-1-ethyl-N-(((1r,4r)-4-(methylsulfonyl)cyclohexyl)methyl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 19
  • [ 1196146-82-3 ]
  • 4-chloro-5-(4-(difluoromethoxy)-6-(3,3,3-trifluoro-2,2-dimethylpropyl)pyridin-3-yl)-1-ethyl-1H-pyrazole-3-carboxylic acid [ No CAS ]
  • 20
  • [ 1196146-82-3 ]
  • 4-chloro-5-(4-(difluoromethoxy)-6-(3,3,3-trifluoro-2,2-dimethylpropyl)pyridin-3-yl)-1-ethyl-N-(((1s,4s)-1-hydroxy-4-(methylsulfonyl)cyclohexyl)methyl)-1H-pyrazole-3-carboxamide [ No CAS ]
  • 21
  • [ 1196146-82-3 ]
  • 4-chloro-5-(4-(difluoromethoxy)-6-(3,3,3-trifluoro-2,2-dimethylpropyl)pyridin-3-yl)-1-ethyl-N-(((1s,4s)-1-hydroxy-4-sulfamoylcyclohexyl)methyl)-1H-pyrazole-3-carboxamide [ No CAS ]
 

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