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Chemical Structure| 85118-00-9 Chemical Structure| 85118-00-9

Structure of 85118-00-9

Chemical Structure| 85118-00-9

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Product Details of [ 85118-00-9 ]

CAS No. :85118-00-9
Formula : C7H5BrF2
M.W : 207.02
SMILES Code : FC1=C(CBr)C(F)=CC=C1
MDL No. :MFCD00000329
InChI Key :LSXJPJGBWSZHTM-UHFFFAOYSA-N
Pubchem ID :581435

Safety of [ 85118-00-9 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P280-P305+P351+P338-P310
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 85118-00-9 ] 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 39.19
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.21
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

2.56
Log Po/w (WLOGP)?

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

3.55
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.

3.95
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

3.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.19

Water Solubility

Log S (ESOL):?

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

-3.11
Solubility 0.159 mg/ml ; 0.000769 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.

-2.21
Solubility 1.28 mg/ml ; 0.0062 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

-4.22
Solubility 0.0125 mg/ml ; 0.0000604 mol/l
Class?

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

Moderately soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

Low
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.

-5.75 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)

1.64

Application In Synthesis of [ 85118-00-9 ]

* 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 [ 85118-00-9 ]

[ 85118-00-9 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 85118-00-9 ]
  • [ 51843-24-4 ]
  • [ 947589-63-1 ]
  • 2
  • [ 85118-00-9 ]
  • [ 53241-92-2 ]
  • [ 1345869-43-3 ]
  • 3
  • [ 936247-35-7 ]
  • [ 85118-00-9 ]
  • [ 534-17-8 ]
  • [ 1609082-28-1 ]
YieldReaction ConditionsOperation in experiment
Example 8A 5-Chloro-3-[(2,6-difluorobenzyl)oxy]-2-nitropyridine 33 g of <strong>[936247-35-7]5-chloro-2-nitropyridin-3-ol</strong> (Example 7A; 189 mmol, 1 equivalent) and 61.6 g of caesium carbonate (189 mmol, 1 equivalent) were initially charged in 528 ml of DMF, 40.4 g of 2,6-difluorobenzyl bromide (189 mmol, 1 equivalent) were added and the mixture was stirred at RT overnight. The reaction mixture was stirred into water/1N aqueous hydrochloric acid. The solid was filtered off, washed with water and air-dried. This gave 54.9 g (97% of theory) of the title compound. 1H-NMR (400 MHz, DMSO-d6): delta=5.46 (s, 2H); 7.22 (t, 2H); 7.58 (q, 1H); 8.28 (d, 1H); 8.47 (d, 1H).
  • 4
  • [ 936247-35-7 ]
  • [ 85118-00-9 ]
  • [ 1609082-28-1 ]
YieldReaction ConditionsOperation in experiment
97% With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; Example 16A 5-Chloro-3-[(2,6-difluorobenzyl)oxy]-2-nitropyridine 33 g of <strong>[936247-35-7]5-chloro-2-nitropyridin-3-ol</strong> (Example 15A; 189 mmol, 1 equivalent) and 61.6 g of caesium carbonate (189 mmol, 1 equivalent) were initially charged in 528 ml of DMF, 40.4 g of 2,6-difluorobenzyl bromide (189 mmol, 1 equivalent) were added and the mixture was stirred at RT overnight. The reaction mixture was stirred into water/1N aqueous hydrochloric acid and the solid was filtered off, washed with water and air-dried. This gave 54.9 g (97% of theory) of the title compound. 1H NMR (400 MHz, DMSO-d6): delta=5.46 (s, 2H); 7.22 (t, 2H); 7.58 (quint., 1H); 8.28 (d, 1H); 8.47 (d, 1H).
97% With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; Example 8A 5-Chloro-3-[(2,6-difluorobenzyl)oxy]-2-nitropyridine 33 g of <strong>[936247-35-7]5-chloro-2-nitropyridin-3-ol</strong> (Example 12A; 189 mmol, 1 equivalent) and 61.6 g of caesium carbonate (189 mmol, 1 equivalent) were initially charged in 528 ml of DMF, 40.4 g of 2,6-difluorobenzyl bromide (189 mmol, 1 equivalent) were added and the mixture was stirred at RT overnight. The reaction mixture was stirred into a water/1N aqueous hydrochloric acid mixture. The solid obtained was filtered off, washed with water and air-dried. This gave 54.9 g (97% of theory) of the title compound. 1H NMR (400 MHz, DMSO-d6): delta=5.46 (s, 2H); 7.22 (t, 2H); 7.58 (q, 1H); 8.28 (d, 1H); 8.47 (d, 1H).
97% With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; Example 13A 5-Chloro-3-[(2,6-difluorobenzyl)oxy]-2-nitropyridine 33 g of <strong>[936247-35-7]5-chloro-2-nitropyridin-3-ol</strong> (Example 12A; 189 mmol, 1 equivalent) and 61.6 g of caesium carbonate (189 mmol, 1 equivalent) were initially charged in 528 ml of DMF, 40.4 g of 2,6-difluorobenzyl bromide (189 mmol, 1 equivalent) were added and the mixture was stirred at RT overnight. The reaction mixture was stirred into water/1N aqueous hydrochloric acid. The solid was filtered off, washed with water and air-dried. This gave 54.9 g (97% of theory) of the title compound. 1H NMR (400 MHz, DMSO-d6): delta=5.46 (s, 2H); 7.22 (t, 2H); 7.58 (q, 1H); 8.28 (d, 1H); 8.47 (d, 1H).
97% With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; 33 g of <strong>[936247-35-7]5-chloro-2-nitropyridin-3-ol</strong> (Example 7A; 189 mmol, 1 equivalent) and 61.6 g of caesium carbonate (189 mmol, 1 equivalent) were initially charged in 528 ml of DMF, 40.4 g of 2,6-difluorobenzyl bromide (189 mmol, 1 equivalent) were added and the mixture was stirred at RT overnight. The reaction mixture was stirred into water/1N aqueous hydrochloric acid. The solid was filtered off, washed with water and air-dried. This gave 54.9 g (97% of theory) of the title compound. 1H-NMR (400 MHz, DMSO-d6): delta=5.46 (s, 2H), 7.22 (t, 2H), 7.58 (q, 1H), 8.28 (d, 1H), 8.47 (d, 1H).
97% With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; Example 8A 5-Chloro-3-[(2,6-difluorobenzyl)oxy]-2-nitropyridine 33 g of <strong>[936247-35-7]5-chloro-2-nitropyridin-3-ol</strong> (Example 7A; 189 mmol, 1 equivalent) and 61.6 g of caesium carbonate (189 mmol, 1 equivalent) were initially charged in 528 ml of DMF, 40.4 g of 2,6-difluorobenzyl bromide (189 mmol, 1 equivalent) were added and the mixture was stirred at RT overnight. The reaction mixture was stirred into water/1 N aqueous hydrochloric acid. The solid was filtered off, washed with water and air-dried. This gave 54.9 g (97% of theory) of the title compound. 1H-NMR (400 MHz, DMSO-d6): delta=5.46 (s, 2H); 7.22 (t, 2H); 7.58 (q, 1H); 8.28 (d, 1H); 8.47 (d, 1H).
97% With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; 33 g of <strong>[936247-35-7]5-chloro-2-nitropyridin-3-ol</strong> (Example 4A;189 mmol, 1 equivalent) and 61.6 g of caesium carbonate(189 mmol, 1 equivalent) were initially charged in 528 ml ofDMF, 40.4 g of 2,6-difluorobenzyl bromide (189 mmol, 1equivalent) were added and the mixture was stirred at RTovernight. The reaction mixture was stirred into water/iNaqueous hydrochloric acid. The solid was filtered off,washed with water and air-dried. This gave 54.9 g (97% oftheory) of the title compound. ?H-NMR (400 MHz, DMSO-d5): oe=5.46 (s, 2H);7.22 (t, 2H); 7.58 (q, 1H); 8.28 (d, 1H); 8.47 (d, 1H).
97% With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; 33 g of <strong>[936247-35-7]5-chloro-2-nitropyridin-3-ol</strong> (Example 1A; 189 mmol, 1 equivalent) and 61.6 g of caesium carbonate (189 mmol, 1 equivalent) were initially charged in 528 ml of DMF, 40.4 g of 2,6-difluorobenzyl bromide (189 mmol, 1 equivalent) were added and the mixture was stirred at RT overnight. The reaction mixture was stirred into water/1N aqueous hydrochloric acid. The solid was filtered off, washed with water and air-dried. This gave 54.9 g (97% of theory) of the title compound. 1H-NMR (400 MHz, DMSO-d6): delta=5.46 (s, 2H); 7.22 (t, 2H); 7.58 (q, 1H); 8.28 (d, 1H); 8.47 (d, 1H).
97% With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; 33 g of <strong>[936247-35-7]5-chloro-2-nitropyridin-3-ol</strong> (Example12A; 189 mmol, 1 equivalent) and 61.6 g of caesium carbonate (189 mmol, 1 equivalent) were initially charged in 528 ml of DMF, 40.4 g of 2,6-difluorobenzyl bromide (189 mmol, 1 equivalent) were added and the mixture was stirred at RT overnight. The reaction mixture was stirred into a mixture of water/iN hydrochloric acid, and the crystals were filtered off with suction, washed with water and air-dried. 54.9 g (97% of theory) of the title compound were obtained. j0377] ?H-NMR (400 MHz, DMSO-d5): oe=5.46 (s, 2H); 7.22 (t, 2H); 7.58 (quint., 1H); 8.28 (d, 1H); 8.47 (d, 1H).

  • 5
  • [ 85118-00-9 ]
  • [ 1254058-34-8 ]
  • [ 4983-28-2 ]
  • [ 1453207-63-0 ]
YieldReaction ConditionsOperation in experiment
17 mg Example 10 To a mixture of 1-(bromomethyl)-2,6-difluorobenzene (14 mg), <strong>[4983-28-2]2-chloro-5-hydroxypyrimidine</strong> (9.1 mg), and N,N-dimethylformamide (1 mL), potassium carbonate (16 mg) was added followed by stirring at room temperature overnight. To the reaction mixture, water was added followed by extraction with chloroform. An organic layer obtained was concentrated under reduced pressure. To the resulting residue, a mixture of 3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]aniline (30 mg), cesium carbonate (65 mg), palladium acetate-X-Phos (Pd:P=1:2) ChemDose (trademark) tablet, and tert-butyl alcohol (0.5 mL) was added followed by stirring at 120° C. overnight under a nitrogen atmosphere. To the reaction mixture, water was added followed by extraction with chloroform. An organic layer obtained was concentrated under reduced pressure. The resulting residue was purified by HPLC (0.1percent aqueous formic acid solution/methanol) to give 5-[(2,6-difluorobenzyl)oxy]-N-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidin-2-amine (17 mg).
 

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