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Chemical Structure| 1158955-21-5 Chemical Structure| 1158955-21-5
Chemical Structure| 1158955-21-5

(2,6-Difluoropyridin-3-yl)(phenyl)methanone

CAS No.: 1158955-21-5

4.5 *For Research Use Only !

Cat. No.: A273767 Purity: 97%

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Product Details of [ 1158955-21-5 ]

CAS No. :1158955-21-5
Formula : C12H7F2NO
M.W : 219.19
SMILES Code : O=C(C1=CC=C(F)N=C1F)C2=CC=CC=C2
MDL No. :MFCD29922059
InChI Key :INYPHEHCTMUQFS-UHFFFAOYSA-N
Pubchem ID :67059736

Safety of [ 1158955-21-5 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H311-H331
Precautionary Statements:P261-P264-P270-P271-P280-P302+P352-P304+P340-P310-P330-P361-P403+P233-P405-P501
Class:6.1
UN#:2810
Packing Group:

Calculated chemistry of [ 1158955-21-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 54.03
TPSA ?

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

29.96 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.05
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

3.06
Log Po/w (WLOGP)?

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

3.43
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.

2.21
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

2.88

Water Solubility

Log S (ESOL):?

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

-3.55
Solubility 0.0618 mg/ml ; 0.000282 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.

-3.36
Solubility 0.0966 mg/ml ; 0.000441 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

-5.06
Solubility 0.00193 mg/ml ; 0.00000879 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

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.

-5.46 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)

2.09

Application In Synthesis of [ 1158955-21-5 ]

* 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 [ 1158955-21-5 ]

[ 1158955-21-5 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 1158955-21-5 ]
  • [ 75-64-9 ]
  • [ 1158955-28-2 ]
  • 2
  • [ 1158955-21-5 ]
  • [ 75-64-9 ]
  • C16H17FN2O [ No CAS ]
  • C16H17FN2O [ No CAS ]
  • 3
  • [ 1513-65-1 ]
  • [ 6919-61-5 ]
  • [ 1158955-21-5 ]
YieldReaction ConditionsOperation in experiment
Reference Example 30; (2,6-Difluoropyridin-3-yl)(phenyl)methanoneTo a solution of 2,6-difluoropyridine (1.0 g, manufactured by Tokyo Chemical Industry Co., Ltd.) in tetrahydrofuran (40 mL, manufactured by Kanto Chemical Co., Inc.), lithium diisopropylamide (23% solution in tetrahydrofuran/ethylbenzene/heptane, 5.79 mL, manufactured by Sigma-Aldrich Corp.) was added dropwise at -78 C., and the mixture was stirred for 30 minutes. Subsequently, N-methoxy-N-methylbenzamide (1.46 mL, manufactured by Sigma-Aldrich Corp.) was further added at the same temperature, and while the temperature was gradually raised to room temperature, the mixture was stirred overnight. A saturated aqueous solution of ammonium chloride (30 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (3×30 mL), washed with brine (30 mL), and dried (MgSO4). The solvent was then evaporated, to give 1.90 g of the title compound. LC-MS: HPLC retention time 1.63 minutes, m/z (M-F+OMe) 232, condition C-1.
  • 4
  • [ 503-29-7 ]
  • [ 1158955-21-5 ]
  • C15H13FN2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
In 1-methyl-pyrrolidin-2-one; at 20℃; for 1h; Reference Example 32; 6-(Azetidin-1-yl)-3-phenyl-1H-pyrazolo[3,4-b]pyridineAzetidine (130 mg, manufactured by Sigma-Aldrich Corp.) was added to a solution of the Reference Example 30 (100 mg) in N-methylpyrrolidone (4.5 mL, manufactured by Kanto Chemical Co., Inc.), and the mixture was stirred for one hour at room temperature. Subsequently, hydrazine hydrate (73 μL, manufactured by Tokyo Chemical Industry Co., Ltd.) was added thereto, and the mixture was stirred overnight at the same temperature. Water (5 mL) was added to the reaction solution, and the mixture was extracted with chloroform (3×10 mL), washed with brine (10 mL), and dried (MgSO4). The solvent was then evaporated, to give 90 mg of the title compound. LC-MS: HPLC retention time 1.22 minutes, m/z (M+H) 251, condition C-1.
  • 5
  • [ 216393-56-5 ]
  • [ 1158955-21-5 ]
  • C24H26FNO2SSi [ No CAS ]
YieldReaction ConditionsOperation in experiment
In 1-methyl-pyrrolidin-2-one; at 20℃; for 1h; Reference Example 34; 3-(3-Phenyl-1H-pyrazolo[3,4-b]pyridin-6-ylthio)phenol3-(Tertiary-butyldimethylsiloxy)thiophenol (548 mg, manufactured by Lancaster Chemical Corp.) was added to a solution of the Reference Example 30 (100 mg) in N-methylpyrrolidone (4.5 mL, manufactured by Kanto Chemical Co., Inc.), and the mixture was stirred for one hour at room temperature. Subsequently, hydrazine hydrate (73 μL, manufactured by Tokyo Chemical Industry Co., Ltd.) was added thereto, and the mixture was stirred overnight at the same temperature. Water (5 mL) was added to the reaction solution, and the mixture was extracted with chloroform (3×10 mL), washed with brine (10 mL), and dried (MgSO4). The solvent was then evaporated, to give 62.3 mg of the title compound. LC-MS: HPLC retention time 1.51 minutes, m/z (M+H) 320, condition C-1.
  • 6
  • [ 2084-18-6 ]
  • [ 1158955-21-5 ]
  • C17H18FNOS [ No CAS ]
YieldReaction ConditionsOperation in experiment
In 1-methyl-pyrrolidin-2-one; at 20℃; for 1h; Reference Example 31; 6-(3-Methylbutan-2-ylthio)-3-phenyl-1H-pyrazolo[3,4-b]pyridine3-Methyl-2-butanethiol (238 mg, manufactured by Wako Pure Chemical Industries, Ltd.) was added to a solution of the Reference Example 30 (100 mg) in N-methylpyrrolidone (4.5 mL, manufactured by Kanto Chemical Co., Inc.), and the mixture was stirred for one hour at room temperature.Subsequently, hydrazine hydrate (73 μL, manufactured by Tokyo Chemical Industry Co., Ltd.) was added thereto, and the mixture was stirred overnight at the same temperature. Water (5 mL) was added to the reaction solution, and the mixture was extracted with chloroform (3×10 mL), washed with brine (10 mL), and dried (MgSO4). The solvent was then evaporated, to give 6.0 mg of the title compound. LC-MS: HPLC retention time 2.12 minutes, m/z (M+H) 298, condition C-1.
 

Historical Records

Technical Information

Categories

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