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Chemical Structure| 380430-49-9 Chemical Structure| 380430-49-9

Structure of 380430-49-9

Chemical Structure| 380430-49-9

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Product Details of [ 380430-49-9 ]

CAS No. :380430-49-9
Formula : C11H16BNO4
M.W : 237.06
SMILES Code : C1=C(NC(OC(C)(C)C)=O)C=CC(=C1)B(O)O
MDL No. :MFCD02093054
InChI Key :UBVOLHQIEQVXGM-UHFFFAOYSA-N
Pubchem ID :3613184

Safety of [ 380430-49-9 ]

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

Computational Chemistry of [ 380430-49-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 6
Fraction Csp3 0.36
Num. rotatable bonds 5
Num. H-bond acceptors 4.0
Num. H-bond donors 3.0
Molar Refractivity 66.51
TPSA ?

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

78.79 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

1.39
Log Po/w (WLOGP)?

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

0.52
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.

0.69
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

-0.86
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.35

Water Solubility

Log S (ESOL):?

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

-2.12
Solubility 1.81 mg/ml ; 0.00764 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.

-2.65
Solubility 0.533 mg/ml ; 0.00225 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

-2.25
Solubility 1.34 mg/ml ; 0.00566 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

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.

-6.76 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)

2.36

Application In Synthesis of [ 380430-49-9 ]

* 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 [ 380430-49-9 ]

[ 380430-49-9 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 180995-12-4 ]
  • [ 380430-49-9 ]
  • [4-(4-chloro-3-cyanopyrid-2-yl)phenyl]carbamic acid tert-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 2.0h; [4-(4-Chloro-3-cyanopyrid-2-yl)phenyl]carbamic acid tert-butyl ester To a solution of 519 mg of <strong>[180995-12-4]2,4-dichloronicotinonitrile</strong> in 25.5 ml of dioxane are added 782 mg of (4-boc-aminophenyl)boronic acid, 693 mg of sodium bicarbonate in 8.5 ml of water and 347 mg of tetrakis(triphenyl-phosphine)palladium. The suspension is stirred at 100 C. for 2 hours under argon. After cooling, the reaction mixture is poured into water and extracted three times with a 90/10 ethyl acetate/methanol solution. The combined organic phases are dried over magnesium sulfate and concentrated under reduced pressure. 1.58 g of crude product are chromatographed on a prepacked Biotage KP-Sil column of 60 A SiO2 32-63 mum (from 0.5/99.5 to 1/99 gradient of solution A in dichloromethane; solution A=38/17/2 dichloromethane/methanol/aqueous ammonia). 797 mg of [4-(4-chloro-3-cyanopyrid-2-yl)phenyl]carbamic acid tert-butyl ester are obtained, the characteristics of which are as follows: MS-EI: 329 (+) IR spectrum (CCl4): 3343; 2981; 2230; 1741; 1524; 1501; 1411; 1392; 1368; 1316; 1220; 1155; 1050 and 844 cm-1 1H NMR spectrum (400 MHz, (CD3)2SO, delta in ppm): 1.50 (s, 9H); 7.62 (d, J=9.0 Hz, 2H); from 7.78 to 7.84 (m, 3H); 8.83 (d, J=5.5 Hz, 1H); 9.67 (s, 1H).
  • 2
  • [ 709652-82-4 ]
  • [ 380430-49-9 ]
  • [ 1267853-94-0 ]
YieldReaction ConditionsOperation in experiment
71% To a microwave reaction vessel were added 4-(tert- butoxycarbonylamino)phenylboronic acid (180 mg, 0.759 mmol), 5-bromo-3-cyano- 2-aminopyridine (170.0 mg, 0.858 mmol), 1,4-dioxane (3.5 mL) and 2M aqueous sodium carbonate (0.94 mL, 1.88 mmol). Argon gas was bubbled through the solution for 5 min, then tetrakis(triphenylphosphine) palladium(O) (40.0 mg, 0.035 mmol) was <n="120"/>added and the vial was sealed and heated in a microwave reactor for 20 min at 170 C. The mixture was partitioned between EtOAc (10 mL) and saturated sodium bicarbonate (10 mL) The aqueous layer was separated and extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with brine (10 mL), dried over MgS04, filtered and concentrated under reduced pressure to give an oil which was purified by silica gel flash chromatography, eluting with 25-100% EtOAc in hexanes. The purified material was dissolved in DCM (4 mL), excess TFA (2 mL) added and the mixture was stirred at rt for 4 h. The mixture was concentrated to dryness, then EtOAc (8 mL), saturated NaHC03 (8 mL) and 1 M aqueous NaOH (1 mL) were added. After confirming basic pH, the layers were shaken and separated and the aqueous layer was extracted with EtOAc (2 x 5 mL). The combined extracts were dried over MgS04, filtered and concentrated under reduced pressure to give 2- amino-5-(4-aminophenyl)nicotinonitrile (113.9 mg, 71%) as a solid, which was sufficiently pure for the next step. LC-MS (ESI) m/z 2 (M +H)+.
  • 3
  • [ 709652-82-4 ]
  • [ 380430-49-9 ]
  • [ 1267849-53-5 ]
 

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