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Structure of 827614-64-2

Chemical Structure| 827614-64-2

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Product Details of [ 827614-64-2 ]

CAS No. :827614-64-2
Formula : C11H17BN2O2
M.W : 220.08
SMILES Code : NC1=NC=C(B2OC(C)(C)C(C)(C)O2)C=C1
MDL No. :MFCD05663837
InChI Key :YFTAUNOLAHRUIE-UHFFFAOYSA-N
Pubchem ID :2756555

Safety of [ 827614-64-2 ]

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

Computational Chemistry of [ 827614-64-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 6
Fraction Csp3 0.55
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 65.12
TPSA ?

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

57.37 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

1.49
Log Po/w (WLOGP)?

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

0.97
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.

0.41
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

0.58
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.69

Water Solubility

Log S (ESOL):?

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

-2.35
Solubility 0.973 mg/ml ; 0.00442 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.

-2.3
Solubility 1.1 mg/ml ; 0.00499 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

-3.27
Solubility 0.118 mg/ml ; 0.000535 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.

-6.58 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)

2.94

Application In Synthesis of [ 827614-64-2 ]

* 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 [ 827614-64-2 ]

[ 827614-64-2 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 827614-64-2 ]
  • [ 445491-71-4 ]
  • [ 1240282-60-3 ]
YieldReaction ConditionsOperation in experiment
91% With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; ethanol; water; at 120℃; for 1.0h;Microwave irradiation; Method 3; 5'-(methylsulfony])-3,3'-bipyridin-6-amineA suspension of 3-bromo-5-(trifluoromethyl)pyridine (2.0 g, 8.40 mmol) 2- Aminopyridine-5-boronic acid pinacol ester (1.94 g, 8.8 mmol), [ 1 , rbis(diphenylphosphino)ferrocene] dichloro-palladium (II) complex with CH2CI2 (136 mg, 0.17 mmol) and sodium carbonate (2.6 g, 25 mmol) in DMEiEbOiEtOH, (7:3:2, 2 mL) was heated to 120 0C for 1 hour minutes in the microwave. After this time the reaction solvents were removed in vacuo and the brown residue redissolved in 2M HCl (30 mL), the aqueous phase was washed with ethyl acetate (3 x 20 mL) and then neutralized with concentrated sodium hydroxide to pH 7.0. Ethyl acetate (20 mL) was added and the title compound collected by filtration and air-dried (1.95 g, 7.6 mmol, 91 %). No further purification was required. LCMS (method A) (M+H+) 250, Rt = 1.65 min
  • 2
  • [ 827614-64-2 ]
  • [ 1120-95-2 ]
  • [ 1243245-89-7 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 90℃; for 10h;Inert atmosphere; Sealed flask; To a sealed flask were added 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)pyridin-2-amine 145-1 (1.54 g, 7 mmol), <strong>[1120-95-2]3-<strong>[1120-95-2]chloropyridazine</strong></strong> 145-2 (0.8 g, 7 mmol), Pd(PPh3)4 (500 mg, 0.7 mmol), toluene (50 mL), ethanol (12 mL) and 2M Na2CO3 (11 mL). The reaction mixture was bubbled with nitrogen for 2 minutes and stirred at 90 °C for 10 hours. After cooled to room temperature, the solvents were evaporated and the residue was redissolved in dichloromethane (200 ml) and treated with IM HCl aqueous solution (50 mL). The two layers were separated and the aqueous layer was treated with 10percent NaOH aqueous solution to adjust the pH to around 13. The resulting solution was evaporated and the remaining solid was exacted with ethyl acetate (100 mL x 3). The combined organic phases were concentrated to give 5- (pyridazin-3-yl)pyridin-2-amine 145-3 as dark brown solid. MS m/z 173.1 (M + 1).
  • 3
  • [ 827614-64-2 ]
  • [ 405939-39-1 ]
  • [ 1444302-80-0 ]
  • 4
  • [ 827614-64-2 ]
  • [ 868066-91-5 ]
  • [ 1567838-03-2 ]
YieldReaction ConditionsOperation in experiment
68% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In ethanol; toluene;Inert atmosphere; Reflux; General procedure: 5-Bromo-2-methylisoindolin-1-one (520 mg, 2.30 mmol) and thiophene-2-boronic acid (442mg, 3.45 mmol) were dissolved in a mixure of toluene (12 mL) and EtOH (6 mL). A solutionof 2 M Na2CO3 (3 mL) and Pd(dppf)Cl2 (94 mg, 0.12 mmol) were added and the entiremixture heated at reflux under N2 for 2 h. Additional thiophene-2-boronic acid (294 mg, 2.30mmol) was added and reflux continued under N2 overnight. Upon cooling, the mixture wasdiluted with water (100 mL) and extracted with CH2Cl2 (6x50 mL). The combined organicfractions were dried (Na2SO4), filtered, and the solvent removed under reduced pressure togive a crude solid which was purified by flash column chromatography on silica gel (EtOAcas eluant). The title compound was isolated as a light-brown solid (510 mg, 97percent).
  • 5
  • [ 827614-64-2 ]
  • [ 23784-96-5 ]
  • 5-((5-chlorothiophen-2-yl)methyl)pyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
44.8% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In water; acetonitrile; at 80℃; for 2h; To a solution of <strong>[23784-96-5]2-chloro-5-(chloromethyl)thiophen</strong>e (0.830 g, 5 mmol), 5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-2-amine (1 .21 g, 5.5 mmol) and potassium carbonate (1 .38 g, 10 mmol) in acetonitrile (24 ml_) and water (6 ml_) was added [1 ,1 '-b/s(diphenylphosphino)ferrocene]dichloropalladium(ll)dichloromethane (0.408 g, 0.5 mmol). Reaction mixture was stirred at 80 C for 2 h and then it was extracted with ethyl acetate (100 ml_ x 2). The combined organic layers were washed with brine (80 ml_), dried over sodium sulfate, filtered and concentrated. The crude residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate = 2/1 ) to give 5-((5-chlorothiophen-2-yl)methyl)pyridin-2-amine as a brown solid (0.600 g, 2.24 mmol, 44.8%); LCMS (ESI) m/z: 225.1 [M+H]+.
44.8% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In water; acetonitrile; at 80℃; for 2h; To a solution of <strong>[23784-96-5]2-chloro-5-(chloromethyl)thiophen</strong>e (0.830 g, 5 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (1.21 g, 5.5 mmol) and potassium carbonate (1.38 g, 10 mmol) in acetonitrile (24 ml_) and water (6 ml_) was added [1,T-b/s(diphenylphosphino)ferrocene]dichloropalladium(ll)dichloromethane (0.408 g, 0.5 mmol). Reaction mixture was stirred at 80 C for 2 h and then it was extracted with ethyl acetate (100 ml_ x 2). The combined organic layers were washed with brine (80 ml_), dried over sodium sulfate, filtered and concentrated. The crude residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate = 2/1) to give 5-((5-chlorothiophen-2-yl)methyl)pyridin-2-amine as a brown solid (0.600 g, 2.24 mmol, 44.8%); LCMS (ESI) m/z: 225.1 [M+H]+.
  • 6
  • [ 827614-64-2 ]
  • [ 885270-32-6 ]
  • 5-(3-chloro-5-methoxybenzyl)pyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In water; acetonitrile; at 80℃; for 1h; General procedure: A mixture of 1 -bromo-3-(bromomethyl)benzene(2.2 g, 8.87 mmol), 5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-2-amine (2.2 g, 10.0 mmol), [1 ,1 '-b/s(diphenylphosphino)ferrocene]dichloropalladium(ll)-dichloromethane complex (0.361 g, 0.44 mmol), potassium carbonate (2.45 g, 17.7 mmol), acetonitrile (80 ml_) and water (16 ml_) was stirred at 80 C under nitrogen for 2 h. The mixture was poured into water, extracted with ethyl acetate (150 ml_ x 2). The combined organic phase was concentrated. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate = 1 /1 ) to afford compound 5-(3-bromobenzyl)pyridin-2-amine (1 .6 g, 6.10 mmol, 68.8%) as a light-yellow oil.
  • 7
  • [ 827614-64-2 ]
  • [ 22282-80-0 ]
  • 2',5'-dimethyl-[3,4'-bipyridin]-6-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.17 g With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; at 80.0℃; for 20.0h; [00214] The title compound (0.17 g) was prepared from 4-chloro-2,5-dimethyl-pyridine (0.50 g, 3.5 mmol, CAS: 22282-80-0), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (0.78 g, 3.5 mmol, CAS: 827614-64-2), Pd(dppf)Cl2 (0.26 g, 0.35 mmol) and sodium carbonate (1.1 g, 10.6 mmol) in accordance with the procedure described for Intermediate 1.1, heating at 80C for 20 h. The crude product was purified by flash column chromatography on the Biotage Isolera OneTM (10 g silica column, eluting 0 - 5% MeOH in DCM) and an SCX cartridge (5 g, washed with MeOH and eluted with 2 M methanolic ammonia).1H NMR (400 MHz, DMSO-d6) δ: 8.29 (s, 1H), 7.96 (d, 1H), 7.47 (dd, 1H), 7.07 (s, 1H), 6.52 (dd, 1H), 6.15 (br s, 2H), 2.43 (s, 3H), 2.22 (s, 3H).
0.17 g With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 80.0℃; for 20.0h;Microwave irradiation; General procedure: [00192] To a stirred suspension of 4-chloro-3,5-dimethyl-pyridine (0.40 g, 2.8 mmol, CAS: 143798-73-6), 4-aminophenylboronic acid hydrochloride (0.59 g, 3.4 mmol, CAS: 80460-73-7) and sodium carbonate (0.96 g, 9.0 mmol) in degassed water (8 mL) and 1,4-dioxane (8 mL) was added Pd(dppf)CI2 (0.21 g, 0.28 mmol) and then heated by microwave irradiation at 120C for 2 h. The reaction mixture was filtered through a pad of Celite and rinsed with EtOAc. The filtrate was washed with brine, dried over MgS04, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (eluting 10 - 30% EtOAc in DCM) to provide the title compound (0.15 g). LCMS (Method 3): 1.42 min, 199.1 [M+H]+
0.17 g With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 80.0℃; for 20.0h;Microwave irradiation; General procedure: [00192] To a stirred suspension of 4-chloro-3,5-dimethyl-pyridine (0.40 g, 2.8 mmol, CAS: 143798-73-6), 4-aminophenylboronic acid hydrochloride (0.59 g, 3.4 mmol, CAS: 80460-73-7) and sodium carbonate (0.96 g, 9.0 mmol) in degassed water (8 mL) and 1,4-dioxane (8 mL) was added Pd(dppf)CI2 (0.21 g, 0.28 mmol) and then heated by microwave irradiation at 120C for 2 h. The reaction mixture was filtered through a pad of Celite and rinsed with EtOAc. The filtrate was washed with brine, dried over MgS04, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (eluting 10 - 30% EtOAc in DCM) to provide the title compound (0.15 g). LCMS (Method 3): 1.42 min, 199.1 [M+H]+
 

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Technical Information

Categories

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