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Structure of 210907-84-9

Chemical Structure| 210907-84-9

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Synonyms: 3-Aminophenylboronic acid pinacol ester

4.5 *For Research Use Only !

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Product Details of [ 210907-84-9 ]

CAS No. :210907-84-9
Formula : C12H18BNO2
M.W : 219.09
SMILES Code : NC1=CC(B(OC2(C)C)OC2(C)C)=CC=C1
Synonyms :
3-Aminophenylboronic acid pinacol ester
MDL No. :MFCD03453668
InChI Key :YMXIIVIQLHYKOT-UHFFFAOYSA-N
Pubchem ID :2734655

Safety of [ 210907-84-9 ]

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

Computational Chemistry of [ 210907-84-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 6
Fraction Csp3 0.5
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 67.32
TPSA ?

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

44.48 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.

1.58
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.

1.13
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

1.12
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.21

Water Solubility

Log S (ESOL):?

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

-2.81
Solubility 0.336 mg/ml ; 0.00153 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.

-2.8
Solubility 0.348 mg/ml ; 0.00159 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

-3.65
Solubility 0.0496 mg/ml ; 0.000226 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

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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.05 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

2.0 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 [ 210907-84-9 ]

* 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 [ 210907-84-9 ]

[ 210907-84-9 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 108-24-7 ]
  • [ 210907-84-9 ]
  • [ 480424-93-9 ]
YieldReaction ConditionsOperation in experiment
78% at 80℃; for 12h; Example 4 N-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetamide through halogen-metal exchange using n-butyllithium at benzhydryliden-(4-bromo-phenyl)-amine The synthetic of 3-aminophenylboronic acid pinacol ester is carried out as described in example 1. After completion of pinacolisation and phase separation the mixture is, however, not concentrated, rather the remaining organic phase is azeotropically dried. The residue, after adding 7.3 g (71.5 mmole) of acetic acid anhydride is stirred at 80 C. for 12 h. Thereafter the bulk of the solvent is removed by distillation and the mixture is cooled to -5 C. Thereby the product crystallizes in the form of colorless crystals and can be isolated by filtration. Thus, 9.37 g (35.9 mmole, 78%) of N-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetamide are obtained. Yield over all steps: 60%.
  • 2
  • [ 32315-10-9 ]
  • [ 35216-39-8 ]
  • [ 210907-84-9 ]
  • [ 1400220-85-0 ]
YieldReaction ConditionsOperation in experiment
Synthesis of l-(3-methanesulfonyl-phenyl)-3-[3-(4,4,5,5-tetramethyl- [l,3,2]dioxaborolan-2-yl)-pheny -urea (intermediate 24)[00431] 3-Methanesulfonyl-phenylamine (0.3 g, 1.44 mmol) was dissolved in 10 mL dichloromethane and diisopropylethylamine (0.376 mL, 2.15 mmol), then solid triphosgene (171 mg, 0.58 mmol) was added. By LCMS (MeOH quench), <10% starting material remained so 3-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-phenylamine (315.5 mg, 1.44 mmol) and diisopropylethylamine (0.276 mL, 1.58 mmol) were added. The reaction was judged complete in lh by LCMS. MeOH (1 mL) was added and the reaction was stirred 18 h. The mixture was washed with DI water, saturated NaHC03, and 1 NHC1 and was dried over MgS04. After concentrtion in vacuo, an off-white solid was obtained. [M+H]+ m/z All.
  • 3
  • trifluoromethylsilver [ No CAS ]
  • [ 210907-84-9 ]
  • [ 325142-82-3 ]
YieldReaction ConditionsOperation in experiment
54% General procedure: An oven-dried Schlenk tube (A) equipped with a magnetic stir bar was charged with AgF (132.2 mg, 1.05 mmol, 3.5 equiv), sealed with a septum, and degassed by alternating vacuum evacuation and nitrogen backfill (three times) before freshly distilled EtCN (3 mL)was added. To the resulting suspension, which was precooled to -78 C (dry ice-acetone bath), was added TMSCF3 (149.3 mg, 1.05 mmol, 3.5 equiv) by microsyringe. The mixture was allowed towarm to r.t. and stirring was continued for an additional 15 min. In due course, AgF solid dissolved and a gray, dark solution of [Ag-CF3] formed. Another Schlenk tube (B) equipped with a magnetic stir bar was charged with the aniline (ArNH2; 0.30 mmol, 1.0 equiv) in freshly distilled EtCN (1.5 mL). To the resulting solution, which was precooled to 0 C (ice bath), aq HCl (12 M; 50.0 muL, 0.60mmol, 2.0 equiv) was added; precipitate formed immediately. After 5 min stirring, t-BuONO (37.7 mg, 0.33 mmol, 1.1 equiv) was added by microsyringe, and the mixture was allowed to stir at 0 C for 15 min. The resulting suspension in Schlenk tube (B) was degassed by alternating vacuum evacuation at -196 C (liquid nitrogen), then the solution was allowed to warm to r.t. under a nitrogen atmosphere (three times), and finally cooled to -78 C (dry ice-acetone bath). The gray, dark solution of [AgCF3] in Schlenk tube (A), which was precooled to -78 C (dry ice-acetone bath), was added to Schlenk tube (B) (ArN2+Cl-) by syringe at -78 C (dry ice-acetone bath) over a period of 1 h. After the addition was complete, the reaction mixture was stirred for 3 h at -78 C (dry ice-acetone bath), allowed to warm to r.t., and stirring was continued for an additional 1 h. An off-white precipitate was observed, and the reaction mixture was diluted with EtOAc (3 mL) and filtered through a short silica gel column. The solvent was removed under reduced pressure with a rotatory evaporator, and the crude residue was purified by silica gel column chromatography to give the desired trifluoromethylation product 3. The yields of products 3a, 3f, 3g, 3l, 3o, 3r, 3x, and 3zb are based on the 19F NMR spectra with 4-F3COC6H4OMe as internal standard. Analytical data for the representative product ethyl 4-(trifluoromethyl)benzoate (3i) are provided below. Data for other products can be found in the literature.
  • 4
  • [ 1211596-82-5 ]
  • [ 210907-84-9 ]
  • 4-(3-aminophenyl)-1H-indole-7-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In tetrahydrofuran; methanol; water; at 70℃; for 24h;Inert atmosphere; A vessel was charged with <strong>[1211596-82-5]4-bromo-1H-indole-7-carboxamide</strong> (2.08 g, 8.70 mmol, Preparation 2), 3- (4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)aniline (2.10 g, 9.57 mmol), sodium carbonate (2.77 g, 26.1 mmol), [1,1 ?-bis(diphenylphosphino)ferrocene] dichloropalladium(II) (0.637 g, 0.870 mmol) and purged with nitrogen. A mixture of THF (71.4 mL), MeOH (10 mL), and water (10 mL) was added and the reaction was stirred at about 70 C for about 24 h. The mixture was filtered through Celite, the solvent was removed under reduced pressure and the residue was purified by column chromatograph on silica gel eluted with MeOH/DCM (0-10%) to provide a solid. The soid was triturated with ether to provide 4-(3-anzinophenyl)-]H-indole-7-carboxanzide (1.37 g, 63%):
  • 5
  • [ 89531-58-8 ]
  • [ 210907-84-9 ]
  • 2-morpholino-N-(3 -(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With triethylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 4h; [0106] To a solution of 3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)aniline, 3- aminophenylboronic acid pinacol ester, (600 mg, 2.74 mmol) and <strong>[89531-58-8]2-morpholinoacetic acid hydrochloride</strong>, morpholineacetic acid HC1 (522 mg, 0.2.88 mmol) in dry DMF (13.7 mL) was added TEA (831 mg, 2.74 mmol, 1.15 mL) followed by HATU (1.04 g, 2.74 mmol) at rt. The mixture was stirred and checked by LC-MS. After 4 h of stirring, the LC-MS showed the reaction was complete. The mixture was poured into water and extracted with EtOAc. The aqueous layer was separated and extracted 2x more with EtOAc. The combined organic layers were washed with water twice and dried over sodium sulfate. The solution was decanted from the drying agent and concentrated in vacuo to give 1.02 g of an off- white solid. The material was dissolved in a minimum amount of DCM and was loaded onto a 24 g column. Column chromatography (10percent EtOAc/Hexanes to 70percent EtOAc/Hexanes gradient) gave 630 mg, 65percent, of an off-white solid as the product. LC-MS shows the correct mass for the product.
 

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