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Chemical Structure| 1408168-76-2 Chemical Structure| 1408168-76-2

Structure of 1408168-76-2

Chemical Structure| 1408168-76-2

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Product Details of [ 1408168-76-2 ]

CAS No. :1408168-76-2
Formula : C7H13BF3KO2
M.W : 236.08
SMILES Code : F[B-](F)(F)CCOC1CCCCO1.[K+]
MDL No. :MFCD22684702
InChI Key :TWXMFURGWHZION-UHFFFAOYSA-N
Pubchem ID :74787645

Safety of [ 1408168-76-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 1408168-76-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 4
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 43.84
TPSA ?

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

18.46 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

2.85
Log Po/w (WLOGP)?

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

3.64
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.

1.47
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

1.02
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.8

Water Solubility

Log S (ESOL):?

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

-2.84
Solubility 0.345 mg/ml ; 0.00146 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.

-2.9
Solubility 0.3 mg/ml ; 0.00127 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

-2.21
Solubility 1.44 mg/ml ; 0.0061 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

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.

-5.72 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)

3.45

Application In Synthesis of [ 1408168-76-2 ]

* 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 [ 1408168-76-2 ]

[ 1408168-76-2 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 909720-21-4 ]
  • [ 1408168-76-2 ]
  • 6-methoxy-2,3-bis(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With palladium diacetate; caesium carbonate; catacxium A; In 1,4-dioxane; water; for 20.0h;Inert atmosphere; Reflux; 1,4-Dioxane (450 mL) and water (150 mL) were added to a mixture of 2,3- dibromo-6-methoxypyridine (12 g, 45 mmol), C2 (31.8 g, 135 mmol), di(l -adamantyl)- ?- butylphosphine (cataCXium A; 3.22 g, 8.98 mmol), palladium(ll) acetate (3.03 g, 13.5 mmol), and cesium carbonate (87.9 g, 270 mmol), and the reaction vessel was evacuated and charged with nitrogen. This evacuation cycle was repeated twice, and the reaction mixture was then stirred at reflux for 20 hours. After the reaction mixture had been partitioned between ethyl acetate (300 mL) and saturated aqueous sodium chloride solution (200 mL), the aqueous layer was extracted with ethyl acetate (2 x 200 mL); the combined organic layers were washed with saturated aqueous sodium chloride solution (200 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was treated with triethylamine (3 mL), dissolved in dichloromethane and treated with silica gel; this mixture was concentrated to dryness and used for silica gel chromatography (Gradient: 0% to 6% ethyl acetate in petroleum ether) to afford the product as a brown oil. Yield: 10 g, 27 mmol, 60%. LCMS m/z 388.0 [M+Na+]. 1H NMR (400 MHz, CDCI3) delta 7.39 (d, J=8.3 Hz, 1H), 6.52 (d, J=8.3 Hz, 1H), 4.63 (dd, J=4.0, 2.8 Hz, 1H), 4.58 (dd, J=4.0, 2.8 Hz, 1H), 4.19-4.1 1 (m, 1H), 3.94-3.71 (m, 4H), 3.89 (s, 3H), 3.58-3.42 (m, 3H), 3.05 (t, J=7.2 Hz, 2H), 2.89 (t, J=7.2 Hz, 2H), 1.86-1.74 (m, 2H), 1.74-1.64 (m, 2H), 1.62-1.44 (m, 8H).
57% With di-(1-adamantyl)-n-butylphosphine; palladium diacetate; caesium carbonate; In 1,4-dioxane; water; at 20 - 100℃; for 20.0h;Inert atmosphere; To a stirred solution of <strong>[909720-21-4]2,3-dibromo-6-methoxypyridine</strong>, Step 1 : Example 31 , (1.4 g, 5.30 mmol), potassium trifluoro(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)borate, Step 3: Example 31 , (3.7 g, 15.90 mmol) and cataCXiumA (0.35 g, 1.06 mmol) in dry 1 ,4 dioxane (12 mL), was added a solution of cesium carbonate (1.62 g, 31.80 mmol) in water (4 mL) at RT. The reaction mixture was degassed for 10 min using N2 gas. Then Pd(OAc)2 (0.33 g, 1.59 mmol) was added at RT and the reaction mixture was heated to 100 ? for 20 h. Completion of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with EtOAc (10mL) and brine (10mL) and the aqueous layer was extracted with EtOAc (2 x 20 mL), washed with water (10 mL), brine (10 ml_), dried over Na2SC>4 and concentrated under reduced pressure. The resulting crude material was purified by flash chromatography using 12-15% EtOAc in petroleum ether to afford the tittle compound. Yield: 57% (1.1 g, brown gummy solid). 1H NMR (400 MHz, CDCI3): d 7.40 (d, J = 8.4 Hz, 1 H), 6.53 (d, J = 8.0 Hz, 1 H), 4.62 (d, J = 20.8 Hz, 2H), 4.20-4.11 (m, 1 H), 3.95-3.89 (m, 2H), 3.88 (s, 3H), 3.81 - 3.70 (m, 2H), 3.61-3.51 (m, 1 H), 3.50-3.46 (m, 2H), 3.07 (t, J = 7.2 Hz, 2H), 2.91 (t, J = 7.2 Hz, 2H), 1.81 (t, J = 8.4 Hz, 2H), 1.71 (t, J = 10.0 Hz, 2H), 1.62-1 .59 (m, 8H). LCMS: (Method A) 366.2 (M+H), 1.7 min, 90.1 % (Max).
 

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