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Structure of 1012085-50-5

Chemical Structure| 1012085-50-5

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Product Details of [ 1012085-50-5 ]

CAS No. :1012085-50-5
Formula : C17H27B2NO4
M.W : 331.02
SMILES Code : CC1(C)C(C)(C)OB(C2=CN=CC(B3OC(C)(C)C(C)(C)O3)=C2)O1
MDL No. :MFCD12923191
InChI Key :PJLRGJDKNWXNRI-UHFFFAOYSA-N
Pubchem ID :56973239

Safety of [ 1012085-50-5 ]

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

Computational Chemistry of [ 1012085-50-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 24
Num. arom. heavy atoms 6
Fraction Csp3 0.71
Num. rotatable bonds 2
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 97.19
TPSA ?

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

49.81 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

2.82
Log Po/w (WLOGP)?

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

1.68
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.

0.47
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

1.28
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.25

Water Solubility

Log S (ESOL):?

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

-3.72
Solubility 0.0628 mg/ml ; 0.00019 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.

-3.52
Solubility 0.0992 mg/ml ; 0.0003 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

-5.2
Solubility 0.00211 mg/ml ; 0.00000637 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

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

Yes
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.

-6.32 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)

3.65

Application In Synthesis of [ 1012085-50-5 ]

* 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 [ 1012085-50-5 ]

[ 1012085-50-5 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 625-92-3 ]
  • [ 73183-34-3 ]
  • [ 1012085-50-5 ]
YieldReaction ConditionsOperation in experiment
With potassium acetate;palladium diacetate; In tetrahydrofuran; for 5h;Reflux; Inert atmosphere;Product distribution / selectivity; Example 3; Synthesis of Compound of Formula IV To a flame dried 3-neck round bottom flask fitted with a condenser, a nitrogen inlet, and a rubber septum was added PcyBiPh (84 mg, 0.20 mmol) and Pd(OAc)2 (19.0 mg, 0.080 mmol). The flask was then protected from the atmosphere and was charged with anhydrous THF (10 mL) and the solution was degassed by purging N2 through the stirred solution. After 15 minutes, the reaction mixture was charged with 3,5-dibromopyridine (0.315 g, 1.33 mmol), pinacolate diborane (0.338 g, 2.66 mmol), dry KOAc (0.217 g, 12.2 mmol), and the mixture was heated at reflux for 5 hours. The reaction mixture was cooled to room temperature and charged with the compound 2, (1.60 g, 3.2 mmol), Na2CO3 (1.20 g, 11.3 mmol), Cs2CO3 (1.10 g, 3.38 mmol), and degassed H2O (0.25 mL). The mixture was then heated at reflux for 20 hours, after which it was cooled to room temperature and concentrated to dryness. The crude material thus obtained was suspended in H2O, collected by filtration, and washed with H2O. The dried solid was chromatographed through SiO2 (3-5% MeOH/CH2Cl2) to give compound of formula IV as a colorless solid. Yield: 0.851 g, 64%. 1H NMR (400 MHz, CD3OD/CD2Cl2, 25 C.) delta7.46 (m, 4H), 7.66 (t, 4H), 7.72 (m, 6H), 7.83 (m, 2H), 7.90 (m, 2H), 8.07 (m, 10H), 8.26 (m, 4H), 8.33 (t, 1H), 8.44 (t, 4H), 8.54 (m, 4H), 8.89 (m, 4H), 8.93 (m, 2H).
With potassium acetate;palladium diacetate; CyJohnPhos; In tetrahydrofuran; for 5h;Inert atmosphere; Reflux; EXAMPLE 3: synthesis of compound of formula IV[0040] To a flame dried 3-neck round bottom flask fitted with a condenser, a nitrogen inlet, and a rubber septum was added PcyBiPh (84 ing, 0.20 mmol) and Pd(OAc)2 (19.0 mg, 0.080 mmol). The flask was then protected from the atmosphere and was charged with anhydrous THF (10 mL) and the solution was degassed by- purging N2 through the stirred solution. After 15 minutes,, the reaction mixture was charged with 3.5-dibromopyridine (0.315 g, 1.33 mmol), pinacolate diborane (0.338 g, 2.66 mmol), dry KOAc (0.217 g, 12.2 mmol), and the mixture was heated at refiux for 5 hours. The reaction mixture was cooled to room temperature and charged with the compound 2, (1.60 g, 3.2 mmol), Na3CO3 (1.20 g, 11.3 mmolX Cs2CO3 (1.10 g, 3.38 mmol). and degassed H2O (0.25 mL). The mixture was then heated at refiux for 20 hours, after which it was cooled to room temperature and concentrated to dryness. The crude materia. thus obtained was suspended in H2O. collected by filtration, and washed with H2O. The dried solid was chromatographed through Sitheta2 (3-5% MeOH/CH2Cl2) to give compound of formula IV as a colorless solid. Yield: 0.851 g, 64%. 1H NMR (400 MH/, CD3OD/CD2Cl2, 25 C) 61.46 Cm, 4H), 7.66 (t, 4H), 7.72 (m, 6H), 7.83 (m, 2H), 7.90 (m, 2H), 8.07 (m, 10H), 8.26 (m, 4H), 8.33 (t, 1H), 8.44 (t, 4H), 8.54 (n% 4H), 8.89 (m, 4H), 8.93 (m, 2H).
With potassium acetate;palladium diacetate; CyJohnPhos; In 1,4-dioxane; at 110℃; for 3h;Inert atmosphere; EXAMPLE 9: synthesis of compound of formula XJ0047J To a schlenk tube was charged 3,5-dibromopyridine (50 mg, 0.21 mmol), pinacolate diborane (0.117 g, 0.462 mmol), dry KOAc (0.1 g, 1 mmol), ligandPCvBin (6.7 mgt 0.0 3 mg, 0.03 mmoL 3%). The schlenk tube was evacuated and filled with argon three times. The schlenk was placed in an argon atmosphere. Anhydrous dioxane (6 tnL) was added. The flask was then heated at 1 K) C for 3 hours under argon atmosphere. Then compound 3 (0.25 g, 0.5 mmol), dry KOAc (0,1 g, 1 mmolX, ligand PCyBin (6.7 mg, 0,017 mmol, 4%) and Pd(OAc)Z (3 nig, 0.013 mmol, 3%) and 5 ml dioxane were added into above reaction solution, then reiluxed at 1 10 X overnight under argon atmosphere. Then cooled to ambient temperature. Distilled water (30 mL) was added via a funnel, and the resulting mixture was filtered on a Bchner funnel. The filtrate was transferred to a separatory funnel and extracted with CIhCh O x 30 mL). The combined organic phases were dried over Na^SO4, filtered on filter paper and concentrated to dryness by rotary evaporation (30 C, 25 mmHg). The resulting yellow solid was purified by column chromatography affording as a white solid 94 mg (45%). 1H NMR (400 MHz, CDCI3) delta 8.94 (m, 6H), 8.64 (m, 4H), 8.20 (m, 1H), 7.97-7.91 (m, 16H). 7.82-7.63 (m, 18H), 7.41 (m, 4H).
  • 2
  • [ 1012085-50-5 ]
  • [ 1233923-09-5 ]
  • C71H47N7 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; caesium carbonate;ligand PCyBiPh; In water; for 20h;Reflux; Inert atmosphere; Example 3; Synthesis of Compound of Formula IV To a flame dried 3-neck round bottom flask fitted with a condenser, a nitrogen inlet, and a rubber septum was added PcyBiPh (84 mg, 0.20 mmol) and Pd(OAc)2 (19.0 mg, 0.080 mmol). The flask was then protected from the atmosphere and was charged with anhydrous THF (10 mL) and the solution was degassed by purging N2 through the stirred solution. After 15 minutes, the reaction mixture was charged with 3,5-dibromopyridine (0.315 g, 1.33 mmol), pinacolate diborane (0.338 g, 2.66 mmol), dry KOAc (0.217 g, 12.2 mmol), and the mixture was heated at reflux for 5 hours. The reaction mixture was cooled to room temperature and charged with the compound 2, (1.60 g, 3.2 mmol), Na2CO3 (1.20 g, 11.3 mmol), Cs2CO3 (1.10 g, 3.38 mmol), and degassed H2O (0.25 mL). The mixture was then heated at reflux for 20 hours, after which it was cooled to room temperature and concentrated to dryness. The crude material thus obtained was suspended in H2O, collected by filtration, and washed with H2O. The dried solid was chromatographed through SiO2 (3-5% MeOH/CH2Cl2) to give compound of formula IV as a colorless solid. Yield: 0.851 g, 64%. 1H NMR (400 MHz, CD3OD/CD2Cl2, 25 C.) delta7.46 (m, 4H), 7.66 (t, 4H), 7.72 (m, 6H), 7.83 (m, 2H), 7.90 (m, 2H), 8.07 (m, 10H), 8.26 (m, 4H), 8.33 (t, 1H), 8.44 (t, 4H), 8.54 (m, 4H), 8.89 (m, 4H), 8.93 (m, 2H).
  • 3
  • [ 1012085-50-5 ]
  • [ 1233923-10-8 ]
  • [ 1197989-81-3 ]
YieldReaction ConditionsOperation in experiment
With potassium acetate;palladium diacetate; In 1,4-dioxane; at 110℃;Reflux; Inert atmosphere; Example 9; Synthesis of Compound of Formula X To a schlenk tube was charged 3,5-dibromopyridine (50 mg, 0.21 mmol), pinacolate diborane (0.117 g, 0.462 mmol), dry KOAc (0.1 g, 1 mmol), ligand PCyBin (6.7 mg, 0.017 mmol, 4%) and Pd(OAc)2 (3 mg, 0.013 mmol, 3%). The schlenk tube was evacuated and filled with argon three times. The schlenk was placed in an argon atmosphere. Anhydrous dioxane (6 mL) was added. The flask was then heated at 110 C. for 3 hours under argon atmosphere. Then compound 3 (0.25 g, 0.5 mmol), dry KOAc (0.1 g, 1 mmol), ligand PCyBin (6.7 mg, 0.017 mmol, 4%) and Pd(OAc)2 (3 mg, 0.013 mmol, 3%) and 5 ml dioxane were added into above reaction solution, then refluxed at 110 C. overnight under argon atmosphere. Then cooled to ambient temperature. Distilled water (30 mL) was added via a funnel, and the resulting mixture was filtered on a Buechner funnel. The filtrate was transferred to a separatory funnel and extracted with CH2Cl2 (3×30 mL). The combined organic phases were dried over Na2SO4, filtered on filter paper and concentrated to dryness by rotary evaporation (30 C., 25 mmHg). The resulting yellow solid was purified by column chromatography affording as a white solid 94 mg (45%). 1H NMR (400 MHz, CDCl3) delta8.94 (m, 6H), 8.64 (m, 4H), 8.20 (m, 1H), 7.97-7.91 (m, 16H), 7.82-7.63 (m, 18H), 7.41 (m, 4H).
With potassium acetate;palladium diacetate; CyJohnPhos; In 1,4-dioxane; at 110℃;Inert atmosphere; EXAMPLE 9: synthesis of compound of formula XJ0047J To a schlenk tube was charged 3,5-dibromopyridine (50 mg, 0.21 mmol), pinacolate diborane (0.117 g, 0.462 mmol), dry KOAc (0.1 g, 1 mmol), ligandPCvBin (6.7 mgt 0.0 3 mg, 0.03 mmoL 3%). The schlenk tube was evacuated and filled with argon three times. The schlenk was placed in an argon atmosphere. Anhydrous dioxane (6 tnL) was added. The flask was then heated at 1 K) C for 3 hours under argon atmosphere. Then compound 3 (0.25 g, 0.5 mmol), dry KOAc (0,1 g, 1 mmolX, ligand PCyBin (6.7 mg, 0,017 mmol, 4%) and Pd(OAc)Z (3 nig, 0.013 mmol, 3%) and 5 ml dioxane were added into above reaction solution, then reiluxed at 1 10 X overnight under argon atmosphere. Then cooled to ambient temperature. Distilled water (30 mL) was added via a funnel, and the resulting mixture was filtered on a Bchner funnel. The filtrate was transferred to a separatory funnel and extracted with CIhCh O x 30 mL). The combined organic phases were dried over Na^SO4, filtered on filter paper and concentrated to dryness by rotary evaporation (30 C, 25 mmHg). The resulting yellow solid was purified by column chromatography affording as a white solid 94 mg (45%). 1H NMR (400 MHz, CDCI3) delta 8.94 (m, 6H), 8.64 (m, 4H), 8.20 (m, 1H), 7.97-7.91 (m, 16H). 7.82-7.63 (m, 18H), 7.41 (m, 4H).
  • 4
  • [ 1012085-50-5 ]
  • [ 1233923-09-5 ]
  • C71H47N7 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; caesium carbonate; In tetrahydrofuran; water; for 20h;Reflux; EXAMPLE 3: synthesis of compound of formula IV[0040] To a flame dried 3-neck round bottom flask fitted with a condenser, a nitrogen inlet, and a rubber septum was added PcyBiPh (84 ing, 0.20 mmol) and Pd(OAc)2 (19.0 mg, 0.080 mmol). The flask was then protected from the atmosphere and was charged with anhydrous THF (10 mL) and the solution was degassed by- purging N2 through the stirred solution. After 15 minutes,, the reaction mixture was charged with 3.5-dibromopyridine (0.315 g, 1.33 mmol), pinacolate diborane (0.338 g, 2.66 mmol), dry KOAc (0.217 g, 12.2 mmol), and the mixture was heated at refiux for 5 hours. The reaction mixture was cooled to room temperature and charged with the compound 2, (1.60 g, 3.2 mmol), Na3CO3 (1.20 g, 11.3 mmolX Cs2CO3 (1.10 g, 3.38 mmol). and degassed H2O (0.25 mL). The mixture was then heated at refiux for 20 hours, after which it was cooled to room temperature and concentrated to dryness. The crude materia. thus obtained was suspended in H2O. collected by filtration, and washed with H2O. The dried solid was chromatographed through Sitheta2 (3-5% MeOH/CH2Cl2) to give compound of formula IV as a colorless solid. Yield: 0.851 g, 64%. 1H NMR (400 MH/, CD3OD/CD2Cl2, 25 C) 61.46 Cm, 4H), 7.66 (t, 4H), 7.72 (m, 6H), 7.83 (m, 2H), 7.90 (m, 2H), 8.07 (m, 10H), 8.26 (m, 4H), 8.33 (t, 1H), 8.44 (t, 4H), 8.54 (n% 4H), 8.89 (m, 4H), 8.93 (m, 2H).
  • 5
  • [ 110-86-1 ]
  • [ 73183-34-3 ]
  • [ 1012085-50-5 ]
  • [ 181219-01-2 ]
  • 6
  • [ 1012085-50-5 ]
  • 3,5-di(indol-3-yl)pyridine [ No CAS ]
  • 7
  • [ 1012085-50-5 ]
  • 1-[2-(3-indolyl)ethyl]-3,5-di(3-indolyl)pyridinium bromide [ No CAS ]
  • 8
  • [ 1012085-50-5 ]
  • 1-ethyl-3,5-di(3-indolyl)pyridinium bromide [ No CAS ]
  • 9
  • 3-bromoindole-1-carboxylic acid tert-butyl ester [ No CAS ]
  • [ 1012085-50-5 ]
  • di-tert-butyl 3,3'-(pyridine-3,5-diyl)bis(1H-indole-1-carboxylate) [ No CAS ]
  • 10
  • [ 110-86-1 ]
  • [ 73183-34-3 ]
  • [ 1012085-50-5 ]
  • [ 329214-79-1 ]
 

Historical Records

Technical Information

Categories

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[ 1012085-50-5 ]

Organoborons

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Pyridines

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