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Chemical Structure| 866100-14-3 Chemical Structure| 866100-14-3

Structure of 866100-14-3

Chemical Structure| 866100-14-3

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Product Details of [ 866100-14-3 ]

CAS No. :866100-14-3
Formula : C15H16B2O4
M.W : 281.91
SMILES Code : CC1(C)C2=C(C3=C1C=C(B(O)O)C=C3)C=CC(B(O)O)=C2
MDL No. :MFCD08704228
InChI Key :LUVUGOUOAXADNE-UHFFFAOYSA-N
Pubchem ID :24820467

Safety of [ 866100-14-3 ]

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

Computational Chemistry of [ 866100-14-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 21
Num. arom. heavy atoms 12
Fraction Csp3 0.2
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 4.0
Molar Refractivity 84.04
TPSA ?

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

80.92 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

2.23
Log Po/w (WLOGP)?

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

-0.65
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.

0.55
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

-0.74
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.

-3.28
Solubility 0.147 mg/ml ; 0.00052 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.

-3.56
Solubility 0.0768 mg/ml ; 0.000273 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

-3.73
Solubility 0.0527 mg/ml ; 0.000187 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

Yes
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.

-6.44 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<0.0
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)

2.84

Application In Synthesis of [ 866100-14-3 ]

* 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 [ 866100-14-3 ]

[ 866100-14-3 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 866100-14-3 ]
  • [ 6091-64-1 ]
  • [ 910893-50-4 ]
YieldReaction ConditionsOperation in experiment
50% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 8h;Heating / reflux; In a stream of argon, 14 g (0.05 mol) of Intermediate 7, 25 g (0.11 mol) of 2-bromobenzoate ethylester, 2.8 g (5 mmol) of tetrakistriphenylphosphinepalladium(0), 200 mL of toluene, and the mixture of 16 g (0.15 mol) of sodium carbonate and 150 mL of water were added to a 1-L three-necked flask, and the whole was refluxed under heat for 8 hours. After the completion of the reaction, an organic layer was washed with water and dried with magnesium sulfate, and then the solvent was removed by distillation with a rotary evaporator. The resultant coarse crystal was recrystallized with ethanol, whereby 12 g of Intermediate 8 (white crystal, 50% yield) as a target were obtained.
50% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 8h;Reflux; Inert atmosphere; (4-3) Synthesis of Intermediate 9; Into a 1 liter three-necked flask, 14 g (0.05 moles) of Intermediate 8, 25 g (0.11 moles) of ethyl 2-bromobenzoate, 2.8 g (5 mmole) of tetrakistriphenylphosphinepalladium(0), 200 ml of toluene and a solution prepared by dissolving 16 g (0.15 moles) of sodium carbonate into 150 ml of water were placed under the stream of argon, and the resultant mixture was heated under the refluxing condition for 8 hours. After the reaction was completed, the organic layer was washed with water and dried with magnesium sulfate, and the solvent was removed by distillation using a rotary evaporator. The obtained crude crystals were recrystallized from ethanol, and 12 g of Intermediate 9 of the object compound was obtained (white crystals; the yield: 50%).
  • 2
  • [ 28320-32-3 ]
  • [ 866100-14-3 ]
YieldReaction ConditionsOperation in experiment
70% In a stream of argon, 35 g (0.1 mol) of Intermediate 6 and 1 L of tetrahydrofuran (THF) were added to a 3-L three-necked flask, and the whole was cooled to - 65C. Subsequently, 220 mL (0.22 mol, 1 mol/L (hexane)) of n-butyllithiumwere slowlyaddedto the resultant. After the reaction liquid had been stirred at - 70C for 6 hours, 45 g (0.24 mol) of boronic triisopropoxide were slowly added to the reaction liquid at - 65C, and the whole was stirred at - 70C for 1 hour. After that, the resultant was stirred at room temperature overnight. After the completion of the reaction, dilute hydrochloric acid was added to the reaction liquid to adjust the pH of the liquid to 3, and an organic layer was separated and washed with a saturated salt solution. After the washed product had been dried with magnesium sulfate, the solvent was removed by distillation with a rotary evaporator, and ethyl acetate was added to the remainder. The resultant crystal was separated by filtration, and was washed with hexane three times, whereby 20 g of Intermediate 7 (white crystal, 70% yield) as a target were obtained.
  • 3
  • [ 5419-55-6 ]
  • [ 28320-32-3 ]
  • [ 866100-14-3 ]
YieldReaction ConditionsOperation in experiment
80% 2,7-dibromo-9,9-dimethylfluorene (14.8 g, 42.4 mmol)Add to three bottles,100 mL of THF was added,Nitrogen protection,-78 deg.] C for 30 minutes,Then, 21 mL of n-butyllithium (2.5 M)Reaction for 1 hour, againAdd triisopropyl borate 14g,Low temperature reaction for 1 hour,Gradually restored room temperature.After the addition of 2M hydrochloric acid to the solution, the pH value of the solution was 4-5, and the aqueous layer was extracted with ethyl acetate. The organic layer was combined and dried to give intermediate A1 (9.5 g, yield 80% ).
70% (4-2) Synthesis of Intermediate 8; Into a 3 liter three-necked flask, 35 g (0.1 mole) of Intermediate 7 and 1 liter of THF were placed under the stream of argon, and the obtained solution was cooled at -65 C. To the cooled solution, 220 ml of a solution of n-butyllithium (0.22 moles, a 1 mole/liter hexane solution) was slowly added. After the reaction fluid was stirred at -70 C. for 6 hours, 45 g (0.24 moles) of boronic acid triisopropoxide was slowly added at -65 C. The resultant fluid was stirred at -70 C. for 1 hour and then at the room temperature for one night. After the reaction was completed, dilute hydrochloric acid was added to the reaction fluid to adjust pH at 3, and the organic layer was separated, washed with a saturated aqueous solution of sodium chloride and dried with magnesium sulfate. The solvent was removed by distillation using a rotary evaporator, and ethyl acetate was added to the residue. The obtained crystals were separated by filtration and washed with hexane three times, and 20 g of Intermediate 8 of the object compound was obtained (white crystals; the yield: 70%).
  • 4
  • [ 866100-14-3 ]
  • [ 910893-51-5 ]
  • 5
  • [ 866100-14-3 ]
  • [ 910893-53-7 ]
  • 6
  • [ 866100-14-3 ]
  • C18H11ClN2 [ No CAS ]
  • C51H34N4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; for 10h;Reflux; A solution of tetraphenylphenylphosphine palladium (2.1 g, 1.83 mmol)And potassium carbonate (75.7 g, 549 mmol)Was added to a solution of intermediate Al (51.6 g, 183 mmol)And intermediate C1 (111.4 g, 384 mmol)In a degassed tetrahydrofuran (500 mL)And the mixture was heated under reflux for 10 hours.The reaction mixture was cooled to room temperature, after which the solvent was removed.The target product TM1 was obtained by silica gel column chromatography(49.5 g, 65% theoretical).
  • 7
  • [ 7647-01-0 ]
  • [ 5419-55-6 ]
  • [ 28320-32-3 ]
  • [ 866100-14-3 ]
YieldReaction ConditionsOperation in experiment
75% Dibromo-9,9-dimethylfluorene (14.9 g, 42.4 mmol) was added to a three-necked flask and 100 mL of THF was added thereto and protected by nitrogen. The mixture was stirred at -78 C for 30 minutes and then n-butyllithium M) 21 mL, reacted for 1 hour, added triisopropyl borate 14 g, reacted at low temperature for 1 hour, and gradually returned to room temperature.In the post-treatment process, 2M hydrochloric acid was added to the system to make the solution have a pH of 4-5, and the mixture was allowed to stand for liquid separation. The aqueous layer was extracted with ethyl acetate, and the organic layers were combined and spin-dry.2,7-Diboronic acid-9,9-dimethylhydrazine (8.9 g, 75% yield) was obtained.
  • 8
  • [ 866100-14-3 ]
  • C22H7BrF4N2 [ No CAS ]
  • C59H26F8N4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; for 4h;Reflux; Tetrakistriphenylphosphine palladium (2.1 g, 1.83 mmol)And potassium carbonate (75.7g, 549mmol) was added to 9,9-dimethyl-fluorene-2,7-diboronic acid (51.4g, 183mmol)And a solution of compound c3 (174.7 g, 384 mmol) in degassed tetrahydrofuran (500 mL)And the mixture was heated under reflux for 4 hours.Hot and suction filtration,Get a lot of solids,Dissolve the solid with a solvent,After concentration,The compound 50 (120.6 g, yield 70%) was obtained by silica gel column chromatography.
  • 9
  • [ 866100-14-3 ]
  • C24H25BrN2S2 [ No CAS ]
  • C63H62N4S4 [ No CAS ]
 

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