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Chemical Structure| 168267-41-2 Chemical Structure| 168267-41-2

Structure of 3,4-Difluorophenylboronic acid
CAS No.: 168267-41-2

Chemical Structure| 168267-41-2

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Product Details of [ 168267-41-2 ]

CAS No. :168267-41-2
Formula : C6H5BF2O2
M.W : 157.91
SMILES Code : C1=C(C=CC(=C1F)F)B(O)O
MDL No. :MFCD00807405
InChI Key :RMGYQBHKEWWTOY-UHFFFAOYSA-N
Pubchem ID :2734337

Safety of [ 168267-41-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319
Precautionary Statements:P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313

Computational Chemistry of [ 168267-41-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 36.18
TPSA ?

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

40.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

1.03
Log Po/w (WLOGP)?

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

0.48
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.

1.15
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

0.13
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.56

Water Solubility

Log S (ESOL):?

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

-1.81
Solubility 2.47 mg/ml ; 0.0156 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.

-1.47
Solubility 5.35 mg/ml ; 0.0339 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

-1.83
Solubility 2.31 mg/ml ; 0.0147 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.

-6.53 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)

2.13

Application In Synthesis of [ 168267-41-2 ]

* 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 [ 168267-41-2 ]

[ 168267-41-2 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 621-38-5 ]
  • [ 168267-41-2 ]
  • <i>N</i>-(3',4'-difluoro-biphenyl-3-yl)-acetamide [ No CAS ]
  • 2
  • [ 79832-89-6 ]
  • [ 168267-41-2 ]
  • [ 134412-17-2 ]
  • 3
  • [ 479691-42-4 ]
  • [ 168267-41-2 ]
  • [ 1567327-00-7 ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; at 95℃;Inert atmosphere; A mixture of tert-butyl 4-(2-chloropyrimidin-4-yl)piperazine-1-carboxylate (10.0g, 33.5mmol), (3,4-difluorophenyl)boronic acid (7.90g, 50.2mmol), 1M aq Na2CO3 (45 mL, 90.0 mmol), tetrakis(triphenylphosphine)palladium (0) (4.6 g, 4.02 mmol), and DME (300 mL) was stirred at 95 C overnight under N2 atmosphere. After cooling to room temperature, the mixture was stirred at room temperature for 15h, diluted with water, and extracted with EtOAc. The organic layer was dried over anhydrous MgSO4, and concentrated in vacuo to give 14 as a brown oil. This product was used for next reaction without further purification.
  • 4
  • [ 7343-33-1 ]
  • [ 168267-41-2 ]
  • 3-bromo-1-(3,4-difluorophenyl)-1,2,4-triazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With pyridine; copper diacetate; In dichloromethane; at 20℃; for 72h;Molecular sieve; Diacetoxycopper (18.4 g, 101.4 mmol), bromo-triazole (lOg, 67.6 mmol), and 4A molecular sieves (250 mg, 0.33 mmol) were mixed in DCM, to which 4-difluorophenyl)boronic acid (14.9g, 94.6 mmol), pyridine (10.9 mL, 135.2 mmol) was added. The mixture was stined at RT under air for 3 days. LCMS showed that no starting material remaining and desired product was formed. The reaction was filtered and the solid was washed with additional DCM (200 ml). The combined organic layer was concentrated with silica gel and dry-loaded to purify on silica gel (240 grams column, 10-90percent ethyl acetate:hexanes) to afford 10.5 g (60percent) of desired product JW3-c. ?H NMR (400 MHz, DMSO-D6) oe 9.30 (s, 1H), 8.08 - 7.96 (m, 1H), 7.77 - 7.62 (m, 2H) ppm. ESI-MS m/z calc. 25 8.95566, found 260.32 (M+1)+; Retention time: 0.96 minutes.
54% With pyridine; In dichloromethane; at 20℃; for 72h;Molecular sieve; Copper(II) acetate (approximately 18.42 g, 101.4 mmol), <strong>[7343-33-1]3-bromo-1H-1,2,4-triazole</strong> (10 g, 67.59 mmol), and 4 A molecular sieves (250 mg/0.33 mmol) were combined in dichloromethane and treated with 3,4-difluorophenyl boronic acid (14.94 g, 94.63 mmol), and pyridine (approximately 10.69 g, 10.93 mL, 135.2 mmol). The mixture was stirred at room temperature under air for 3 days. The reaction was filtered and the solid was washed with additional dichloromethane (200 mL). The combined organic layers were concentrated with silica gel and dry-loaded to purify on silica gel to afford 3-bromo-1-(3,4-difluorophenyl)-1,2,4-triazole (10.5 g, 54percent). MR (400 MHz, DMSO-^e) delta 9.30 (s, 1H), 8.08 - 7.96 (m, 1H), 7.77 - 7.62 (m, 2H) ppm. ESI-MS m/z calc. 258.95566, found 260.32 (M+l)+; Retention time: 0.96 minutes.
  • 5
  • [ 20358-03-6 ]
  • [ 168267-41-2 ]
  • 2-amino-5-(3,4-difluorophenyl)benzothiazole [ No CAS ]
  • 6
  • [ 39549-79-6 ]
  • [ 168267-41-2 ]
  • 2-(3,4-difluorophenyl)-7-methyl-2,3-dihydrobenzo[d][1,3,2]diazaborinin-4(1H)-one [ No CAS ]
  • 7
  • [ 885588-14-7 ]
  • [ 168267-41-2 ]
  • methyl 2-(3,4-difluorophenyl)-5-fluoroisonicotinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; at 100℃; for 16.0h;Inert atmosphere; A mixture of compound <strong>[885588-14-7]methyl 2-bromo-5-fluoroisonicotinate</strong> (110 g, 470.04 mmol, 1.0 eq.), (3,4-difluorophenyl)boronic acid (111.34 g, 705.06 mmol, 1.5 eq), Pd(dppf)Cl2 (8.60 g, 11.75 mmol, 0.025 eq) and potassium carbonate (129.92 g, 940.08 mmol, 2.0 eq) in 1,4-dioxane (1. Pd(dppf)Cl21 L) was heated to 100C for 16 hours under N2. The mixture was diluted with H2O (500 mL) and EtOAc(1.3 L) and stirred for 15 mins. The organic layer was separated, washed with brine (500 mL), dried over Na2SO4 and concentrated, the residue purified by combi-flash (5%~50% EtOAcin PE) and trituration (PE:EA=50/1, 100 mL) to afford methyl 2-(3,4- difluorophenyl)-5-fluoroisonicotinate (Intermediate A).1H NMR (CDCl3400MHz): d 8.56 (d, J=2.0 Hz, 1H), 8.05 (d, J=5.6 Hz, 1H), 7.79 (ddd, J=2.4, 8.4, 10.8 Hz, 1H), 7.64 (td, J=2.8, 8.8 Hz, 1H), 7.26 - 7.11 (m, 1H), 3.94 (s, 3H).
 

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