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Structure of 126120-87-4

Chemical Structure| 126120-87-4

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Product Details of [ 126120-87-4 ]

CAS No. :126120-87-4
Formula : C7H5BF2O4
M.W : 201.92
SMILES Code : OB(O)C1=CC=CC2=C1OC(F)(F)O2
MDL No. :MFCD08062343
InChI Key :GCIIKWAIWSFGLA-UHFFFAOYSA-N
Pubchem ID :16427145

Safety of [ 126120-87-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 126120-87-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 6.0
Num. H-bond donors 2.0
Molar Refractivity 42.47
TPSA ?

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

58.92 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

1.41
Log Po/w (WLOGP)?

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

0.53
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.

-0.24
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

-0.28
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.28

Water Solubility

Log S (ESOL):?

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

-2.23
Solubility 1.19 mg/ml ; 0.00587 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.

-2.25
Solubility 1.13 mg/ml ; 0.0056 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

-1.59
Solubility 5.14 mg/ml ; 0.0255 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

No
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

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)

2.83

Application In Synthesis of [ 126120-87-4 ]

* 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 [ 126120-87-4 ]

[ 126120-87-4 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 1583-59-1 ]
  • [ 121-43-7 ]
  • [ 110-18-9 ]
  • [ 126120-87-4 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; n-butyllithium; sodium chloride; In tetrahydrofuran; Petroleum ether; Step F Preparation of (2,2-difluoro-1,3-benzodioxol-4-yl)boronic acid A solution of n-butyllithium (5.57 mL of a 2.5M solution in hexanes, 13.9 mmol) was added to dry tetrahydrofuran (75 mL) at room temperature under a nitrogen atmosphere. The resulting solution was cooled to -15 C. and N,N,N',N'-tetramethylenediamine (2.10 mL, 13.9 mmol) was added dropwise. The reaction was stirred at -15 C. for 0.5 h and then <strong>[1583-59-1]2,2-difluoro-1,3-benzodioxole</strong> was added dropwise while maintaining the reaction temperature below -10 C. After the addition was complete, the reaction was stirred at -15 C. for 1 h before a solution of trimethylborate (1.58 mL, 13.9 mmol) in dry tetrahydrofuran (5 mL) was added dropwise while maintaining the reaction temperature below -10 C. The reaction mixture was stirred at -10 C. for 1 h and then allowed to come to room temperature while stirring overnight. To the reaction mixture was added a 1N solution of hydrochloric acid and then concentrated hydrochloric acid until the solution was strongly acidic. The acidic solution was poured into water. The resulting mixture was saturated with sodium chloride and extracted with diethyl ether three times. The combined organic extracts were dried (MgSO4), filtered, and concentrated under reduced pressure to give a dark-brown oil. The oil was suspended in boiling petroleum ether and the hot solution filtered to remove a small amount of brown solid. The filtrate was then cooled and filtered to obtain a light-gray solid. The filtrate was concentrated under reduced pressure to give a light-brown solid which was combined with the gray solid obtained from recrystallization to afford the title compound of Step F (1.28 g, 50%). 1 H NMR (CDCl3): delta4.92 (s,2H), 7.15 (m,2H), 7.5 (d, 1H). 19 F NMR (CDCl3): delta-50.33 (s,2F).
  • 2
  • [ 1583-59-1 ]
  • [ 121-43-7 ]
  • [ 126120-87-4 ]
YieldReaction ConditionsOperation in experiment
Intermediate 195(2,2-difluoro-l,3-benzodioxol-4-yl)boronic acid2,2-Difluoro-l,3-benzodioxole (960 mg, 6.1 mmol) was dissolved in THF (8 mL) and cyclohexane (4 mL) and the resulting solution cooled to -78 C. sec-BuLi 1.4M solution in cyclohexane (4.3 mL, 6.1 mmol) was added dropwise and the reaction mixture stirred for 1.5 hours at -78C. Trimethylborate (694 mg, 6.75 mmol) was added and the mixture was allowed to warm slowly to -30 C. The reaction mixture was quenched with a 2N solution of HCI and diluted with ethyl acetate. Two phases were separated and the organic layer was washed twice with brine, dried over Na2S04 and evaporated to dryness affording the title compound as yellow oil which was used in the next step without further purification. 1H-NMR (400 MHz, DMSO-d6 + D20): delta ppm 7.39 (1H, dd), 7.34 (1H, dd), 7.14 (t, 1H, 7=7.90 Hz). 19F-NMR (376 MHz, DMSO-d6 + D20): delta ppm -48.92. 13C-NMR (200 MHz, DMSO-d6 + D20): delta ppm 147.3, 142.8, 131.6 (t, 7=250.7 Hz), 130.1, 124.3, 112.0
2,2-Difluoro-l,3-benzodioxole (960 mg, 6.1 mmol) was dissolved in THF (8 mL) and cyclohexane (4 mL) and the resulting solution cooled to -78 C. sec-BuLi 1.4M solution in cyclohexane (4.3 mL, 6.1 mmol) was added dropwise and the reaction mixture stirred for 1.5 hours at -78C. Trimethylborate (694 mg, 6.75 mmol) was added and the mixture was allowed to warm slowly to -30 C. The reaction mixture was quenched with a 2N solution of HCI and diluted with ethyl acetate. Two phases were separated and the organic layer was washed twice with brine, dried over Na2S04 and evaporated to dryness affording the title compound as yellow oil which was used in the next step without further purification. 1H-NM (400 M Hz, DMSO-d6 + D20): delta ppm 7.39 (1H, dd), 7.34 (1H, dd), 7.14 (t, 1H,7=7.90 Hz). 19F-NMR (376 MHz, DMSO-d6 + D20): delta ppm -48.92. 13C-NMR (200 M Hz, DMSO-d6 + D20): delta ppm 147.3, 142.8, 131.6 (t, 7=250.7 Hz), 130.1, 124.3, 112.0
2,2-Difluoro-1,3-benzodioxole (960 mg, 6.1 mmol) was dissolved in THF (8 mL) and cyclohexane (4 mL) and the resulting solution cooled to -78 C. sec-BuLi 1.4M solution in cyclohexane (4.3 mL, 6.1 mmol) was added dropwise and the reaction mixture stirred for 1.5 hours at -78 C. Trimethylborate (694 mg, 6.75 mmol) was added and the mixture was allowed to warm slowly to -30 C. The reaction mixture was quenched with a 2N solution of HCl and diluted with ethyl acetate. Two phases were separated and the organic layer was washed twice with brine, dried over Na2SO4 and evaporated to dryness affording the title compound as yellow oil which was used in the next step without further purification. 1H-NMR (400 MHz, DMSO-d6+D2O): delta ppm 7.39 (1H, dd), 7.34 (1H, dd), 7.14 (t, 1H, J=7.90 Hz). 19F-NMR (376 MHz, DMSO-d6+D2O): delta ppm -48.92. 13C-NMR (200 MHz, DMSO-d6+D2O): delta ppm 147.3, 142.8, 131.6 (t, J=250.7 Hz), 130.1, 124.3, 112.0
  • 3
  • [ 1583-59-1 ]
  • [ 126120-87-4 ]
YieldReaction ConditionsOperation in experiment
Intermediate 195 (2,2-difluoro-1,3-benzodioxol-4-yl)boronic acid [1074] [1075] 2,2-Difluoro-1,3-benzodioxole (960 mg, 6.1 mmol) was dissolved in THF (8 mL) and cyclohexane (4 mL) and the resulting solution cooled to -78 C. sec-BuLi 1.4M solution in cyclohexane (4.3 mL, 6.1 mmol) was added dropwise and the reaction mixture stirred for 1.5 hours at -78 C. Trimethylborate (694 mg, 6.75 mmol) was added and the mixture was allowed to warm slowly to -30 C. The reaction mixture was quenched with a 2N solution of HCl and diluted with ethyl acetate. Two phases were separated and the organic layer was washed twice with brine, dried over Na2SO4 and evaporated to dryness affording the title compound as yellow oil which was used in the next step without further purification. [1076] 1H NMR (400 MHz, DMSO-d6+D2O): delta ppm 7.39 (1H, dd), 7.34 (1H, dd), 7.14 (t, 1H, J=7.90 Hz). 19F-NMR (376 MHz, DMSO-d6+D2O): delta ppm -48.92. 13C-NMR (200 MHz, DMSO-d6+D2O): delta ppm 147.3, 142.8, 131.6 (t, J=250.7 Hz), 130.1, 124.3, 112.0
  • 4
  • [ 1583-59-1 ]
  • [ 121-43-7 ]
  • [ 7732-18-5 ]
  • [ 126120-87-4 ]
YieldReaction ConditionsOperation in experiment
84.82% 2,2-Difluoro-1 ,3-benzodioxole (3 g, 18.98 mmol) was dissolved in TBF(60 mL) and the resulting solution cooled to -78 oc. Sec-butyllithium (1.3M, 15 mL) wasadded dropwise and the reaction mixture stirred for 1.5 h at -78 oc. Trimethyl borate (2.44mL, 21.63 mmol) was added and the mixture was allowed to warm slowly to -30 oc for lh.The reaction mixture was quenched with 2N solution of HCl, adjusted to pH .~ 2-3 anddiluted with H20 (30 mL). The reaction was extracted with EA (200 mL), two phases wereseparated and the organic layer was washed with brine (1 00 mL), dried over Na2S04, filteredand evaporated to dryness. Compound 107A (3.25 g, yield 84.82(%) was obtained as a whitesolid, which was used for next step without purification. 1H NMR (400 MHz, DMSO-d6) 88.44 (br s, 2B), 7.42 (del, J "' 7.8, 15.3 Hz, 2H), 7.23-7.12 (m, lEI).
 

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