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Chemical Structure| 871125-82-5 Chemical Structure| 871125-82-5

Structure of 871125-82-5

Chemical Structure| 871125-82-5

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Product Details of [ 871125-82-5 ]

CAS No. :871125-82-5
Formula : C13H12BFO3
M.W : 246.04
SMILES Code : FC1=CC=C(C=C1)COC2=CC=C(B(O)O)C=C2
MDL No. :MFCD07784403
InChI Key :HNQLLMVLGZJPJT-UHFFFAOYSA-N
Pubchem ID :16218069

Safety of [ 871125-82-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 871125-82-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 12
Fraction Csp3 0.08
Num. rotatable bonds 4
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 67.2
TPSA ?

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

49.69 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

2.39
Log Po/w (WLOGP)?

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

1.35
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.

1.94
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

1.18
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.37

Water Solubility

Log S (ESOL):?

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

-3.1
Solubility 0.195 mg/ml ; 0.000793 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.

-3.07
Solubility 0.207 mg/ml ; 0.000842 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

-4.24
Solubility 0.0143 mg/ml ; 0.0000581 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

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.

-6.1 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)

2.07

Application In Synthesis of [ 871125-82-5 ]

* 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 [ 871125-82-5 ]

[ 871125-82-5 ] Synthesis Path-Downstream   1~21

  • 1
  • [ 1225276-07-2 ]
  • [ 871125-82-5 ]
  • [ 1225276-52-7 ]
YieldReaction ConditionsOperation in experiment
With nickel(II) iodide; trans-2-aminocyclohexan-1-ol; sodium hexamethyldisilazane; In isopropyl alcohol; at 70℃;Inert atmosphere; Example 40; Synthesis of N-(3,4-dimethylisoxazol-5-yl)-2-{4-[(4-fluorobenzyl)oxy]phenyl}-7-azaspiro[3.5]nonane-7-carboxamide A 0.4 M stock solution of 2-bromo-7-aza-spiro[3.5]nonane-7-carboxylic acid tert-butyl ester in anhydrous isopropanol (0.5 mL, 0.200 mmol) and a 0.024 M stock solution of trans 2-aminocyclohexanol in isopropanol (0.5 mL, 0.012 mmol, 0.06 equiv) was added to a vial containing sodium hexamethyldisilazide (0.400 mmol, 2 equiv), nickel iodide (0.012 mmol, 0.06 equiv), and <strong>[871125-82-5]{4-[(4-fluorobenzyl)oxy]phenyl}boronic acid</strong> (0.400 mmol, 2 equiv; CAS No.871125-82-5). The vial was flushed with nitrogen, capped, and shook at 70 C. overnight. The reaction mixtures were concentrated under vacuum to give the crude tert-butyl carbamate derivative. The residue was dissolved in dichloromethane (1.2 mL) and treated with 4 N HCl in dioxane (0.8 mL). After shaking for 2 h, the reaction mixture was concentrated under vacuum to give the crude amine hydrochloride salt derivative. The crude amine hydrochloride salt residue was dissolved in acetonitrile (2.0 mL) and split into two separate vials (1.0 mL, 0.1 mmol each). To the solution in one of the vials was added diisopropylethylamine (0.17 mL, 1.0 mmol, 10 equiv) followed by a solution of phenyl(3,4-dimethylisoxazol-5-yl)carbamate (0.120 mmol in acetonitrile, 1.2 equiv). After shaking overnight at rt, the reaction was concentrated under vacuum, diluted in DMSO (1.5 mL), filtered through celite, and purified by reverse phase HPLC (acetonitrile/water/0.05% trifluoroacetic acid) to give the title compound (8.5 mg). LCMS (Phenomenex Gemini C18 4.6×50 mm 5 mum (0.04% Formic Acid, 0.01% TFA/MeCN)) tR 2.23 min; m/z 464.45 (MH+).
  • 2
  • [ 871125-82-5 ]
  • [ 1235868-29-7 ]
  • C28H25NO5 [ No CAS ]
  • 3
  • [ 871125-82-5 ]
  • [ 1256286-01-7 ]
  • [ 1320362-21-7 ]
  • 4
  • [ 645-00-1 ]
  • [ 871125-82-5 ]
  • [ 1345691-24-8 ]
  • 7
  • [ 871125-82-5 ]
  • [ 585-79-5 ]
  • [ 1345691-24-8 ]
  • 8
  • [ 106-43-4 ]
  • [ 871125-82-5 ]
  • [ 449737-45-5 ]
  • 9
  • [ 871125-82-5 ]
  • 3-amino-N-(4-(trifluoromethyl)phenyl)thiophene-2-carboxamide [ No CAS ]
  • 3-((4-((4-fluorobenzyl)oxy)phenyl)amino)-N-(4-(trifluoromethyl)phenyl)thiophene-2-carboxamide [ No CAS ]
  • 10
  • [ 871125-82-5 ]
  • N-(4-fluorobenzyl) 3-aminothiophene-2-carboxamide [ No CAS ]
  • N-(4-fluorobenzyl)-3-((4-((4-fluorobenzyl)oxy)phenyl)amino)thiophene-2-carboxamide [ No CAS ]
  • 11
  • [ 728033-97-4 ]
  • [ 871125-82-5 ]
  • 3-((4-((4-fluorobenzyl)oxy)phenyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide [ No CAS ]
  • 12
  • [ 871125-82-5 ]
  • N-(4-fluorophenyl) 3-aminothiophene-2-carboxamide [ No CAS ]
  • 3-((4-((4-fluorobenzyl)oxy)phenyl)amino)-N-(4-fluorophenyl)thiophene-2-carboxamide [ No CAS ]
  • 13
  • [ 871125-82-5 ]
  • [ 1354745-85-9 ]
  • 6-chloro-3-(4-(4-fluorobenzyloxy)phenyl)-7-methoxy-2-methylquinolin-4(1H)-one [ No CAS ]
  • 14
  • [ 871125-82-5 ]
  • (S)-ethyl 2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate [ No CAS ]
  • (S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((4-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid [ No CAS ]
  • 15
  • [ 871125-82-5 ]
  • (S)-ethyl 2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate [ No CAS ]
  • (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((4-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
59.9% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In N,N-dimethyl-formamide; at 100 - 110℃; for 1.5h; 10090] A mixture of (S)-ethyl 2-(5-bromo-4-(4,4-dimeth- ylpiperidin- 1 -yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy) acetate (0.049 g, 0.108 mmol), (4-((4-fluorobenzyl)oxy)phe- nyl)boronic acid (0.040 g, 0.161 mmol) and 2M Na2CO3 (0.134 ml, 0.269 mmol) in DMF (2 mE) was degassed for 10 mm. Then, Pd(Ph3P)4 (0.012 g, 10.76 tmol) was added, degassed for 5 mm and placed in a pre-heated oil bath at 100 C. After 1.5 h at 110 C., cooled and purified by prep-HPEC to afford (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperi- din-i -yl)-5-(4-((4-fluorobenzyl)oxy)phenyl)-2,6-dimeth- ylpyridin-3-yl)acetate (0.0372 g, 0.065 mmol, 59.9% yield) as tan color solid. LCMS (M+H)=577.6.
  • 16
  • [ 871125-82-5 ]
  • C46H60FN3O4 [ No CAS ]
  • 17
  • [ 871125-82-5 ]
  • C13H10FN3O [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium azide; copper(II) sulfate; In methanol; General procedure: The compounds (3-34) were prepared by NaN3 (1.2 equiv.), CuSO4 (0.1 equiv), and boronic acids (1.2 equiv) in methanol (10 mL) were allowed to react for 1-4 h, followed by addition of water (10 mL), sodium ascorbate (0.5 equiv), and propargylated betulinic ester (1.0 equiv) ( Scheme 1 ). The contents were stirred vigorously at room temperature for 6-8 h (as monitored by TLC analysis). After completion of the reaction, the contents diluted with water and extracted with ethyl acetate three times. The combined ethyl acetate extract was washed with brine, dried over anhydrous Na2SO4 and evaporated under reduced pressure on a rota vapour. The crude product obtained thus subjected was put to column chromatography (silica gel) with appropriate EtOAc: Hexane mixture as eluent to afford the desired pure products in good yields. All the synthesized compounds were characterized by 1H NMR, 13C NMR, IR and HRMS spectroscopic analysis.
  • 18
  • [ 934-32-7 ]
  • [ 871125-82-5 ]
  • N-(4-((4-fluorobenzyl)oxy)phenyl)-1H-benzo[d]imidazol-2-amine [ No CAS ]
  • 19
  • [ 871125-82-5 ]
  • 6-bromo-4-(4-cyanomethylphenylamino)quinazoline [ No CAS ]
  • 6-(4-fluorobenzyloxyphen-4-yl)-4-(4-cyanomethylphenylamino)quinazoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 90℃; for 12.0h;Inert atmosphere; General procedure: A solution of 2 M K2CO3 solution (3 ml) in dioxane (3 ml) wastaken in round bottom flask and was purged with nitrogen balloonfor 5 min at room temperature. A mixture of boronic acid(1.2 mmol) and compound 15 (0.1 g, 1 mmol) was added to thisreaction mixture, and it was again purged with nitrogen for 5 min.Pd(PPh3)4 (0.05 mmol) was then added, followed by purging andallowed the reaction mixture to stir at 90 C for overnight. Aftercompletion of the reaction, product was extracted with ethyl acetate(2 50 ml). The combined organic layer was concentrated invacuo and crude reaction mixture was purified by silica gel(100e200) column chromatography using EtOAc: hexane aseluent to get desired products 9a-x.
  • 20
  • [ 871125-82-5 ]
  • (S)-ethyl 2-(5-bromo-2,6-dimethyl-4-(p-tolyl)pyridin-3-yl)-2-(tert-butoxy)acetate [ No CAS ]
  • (S)-ethyl 2-(tert-butoxy)-2-(5-(4-((4-fluorobenzyl)oxy)phenyl)-2,6-dimethyl-4-(p-tolyl)pyridin-3-yl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.10113 g With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In N,N-dimethyl-formamide; at 110℃; for 8.0h; A mixture of (S)-ethyl 2-(5 -bromo-2,6-dimethyl-4-(p-tolyl)pyridin-3 -yl)-2-(tert-butoxy)acetate (0.03 g, 0.069 mmol), (4-((4- fluorobenzyl)oxy)phenyl)boronic acid (0.034 g, 0.138 mmol) and 2MNa2CO3 (0.069 ml, 0.138 mmol) in DMF (2 mL) degassed for 10 mm. Then, Pd(Ph3P)4 (7.98 mg, 6.91.imol) was added, degassed for 5 mm and placed in a pre-heated oil bath at 110 C. After8 h, cooled and purified by prep-HPLC to afford (S)-ethyl 2-(tert-butoxy)-2-(5-(4-((4-fluorobenzyl)oxy)phenyl)-2,6-dimethyl-4-(p-tolyl)pyridin-3 -yl)acetate (0.10113 g, 0.182mmol, 264 % yield) as purple solid. ?H NMR (500MHz, CDC13) oe 7.41 - 7.36 (m, 2H),7.20 (dd, J7.7, 1.7 Hz, 1H), 7.11 -7.06 (m, 4H), 6.90-6.84 (m, 2H), 6.71 -6.63 (m,3H), 5.00 (s, 1H), 4.97 (s, 2H), 4.30 - 4.15 (m, 2H), 2.70 (s, 3H), 2.34 (s, 3H), 2.29 (s,3H), 1.30 (t, J=7.2 Hz, 3H), 0.96 (s, 9H). LCMS (M+H) = 556.4.
  • 21
  • [ 871125-82-5 ]
  • (S)-ethyl 2-(5-bromo-2,6-dimethyl-4-(p-tolyl)pyridin-3-yl)-2-(tert-butoxy)acetate [ No CAS ]
  • (S)-2-(tert-butoxy)-2-(5-(4-((4-fluorobenzyl)oxy)phenyl)-2,6-dimethyl-4-(p-tolyl)pyridin-3-yl)acetic acid [ No CAS ]
 

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