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Structure of 78760-60-8

Chemical Structure| 78760-60-8

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Product Details of [ 78760-60-8 ]

CAS No. :78760-60-8
Formula : C13H10N2O
M.W : 210.23
SMILES Code : N#CC1=CC=C(OCC2=CC=CC=C2)C=N1
MDL No. :MFCD11977436
InChI Key :FCECYLUEYDBZHV-UHFFFAOYSA-N
Pubchem ID :15574701

Safety of [ 78760-60-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H312-H332
Precautionary Statements:P280

Computational Chemistry of [ 78760-60-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 12
Fraction Csp3 0.08
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 59.93
TPSA ?

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

45.91 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

2.24
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

2.37
Log Po/w (WLOGP)?

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

2.38
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.

1.07
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

2.84
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.18

Water Solubility

Log S (ESOL):?

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

-2.99
Solubility 0.213 mg/ml ; 0.00101 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.

-2.97
Solubility 0.223 mg/ml ; 0.00106 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

-4.78
Solubility 0.00349 mg/ml ; 0.0000166 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

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

Yes
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

Yes
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.

-5.9 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

0.0 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)

2.23

Application In Synthesis of [ 78760-60-8 ]

* 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 [ 78760-60-8 ]

[ 78760-60-8 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 41960-47-8 ]
  • [ 100-51-6 ]
  • [ 78760-60-8 ]
  • 2
  • 5-hydroxypyridine-2-carbonitrile [ No CAS ]
  • [ 100-39-0 ]
  • [ 78760-60-8 ]
YieldReaction ConditionsOperation in experiment
85% Step l:5-Benzyloxy-pyridine-2-carbonitrile (3_60_2) [00482] A mixture of 5-hydroxy-pyridine-2-carbonitrile 3_60_1 (14 g, 116 mmol) and potassium carbonate (32.2 g, 233 mmol) in Nu,Nu-dimethylformamide (140 mL) was heated at 60C for 0.5 hours. Benzylbromide (13.9 g, 116 mmol) was added and the mixture was stirred at 66C for 1 hour, and filtered and the filtrate was concentrated, extracted with ethyl acetate, washed with brine, dried over sodium sulfate and concentrated. The residue was triturated with diethyl ether and hexanes to give a precipitate, which was collected to give compound 3_60_2 (21 g, 85 % yield) as a solid. [00483] NMR (400 MHz, DMSO-d6): delta = 5.27 (s, 2H), 7.33-7.50 (m, 5H), 7.65 (dd, J=8.8, 2.9 Hz, 1H), 8.00 (d, J = 8.6 Hz, 1H), 8.50 (d, J = 3.2 Hz, 1H).
  • 3
  • [ 78760-60-8 ]
  • [ 1448674-60-9 ]
YieldReaction ConditionsOperation in experiment
10 g With n-butyllithium; 1,1,1,3,3,3-hexamethyl-disilazane; In tetrahydrofuran; hexane; at 0 - 20℃; for 16h; Step 2:5-Benzyloxy-pyridine-2-carboxamidine (3_60_3) [00484] Butyllithium (1.6N in hexane, 168 mL, 269 mmol) was added to a solution of hexamethyldisilazane (56.5 mL, 269 mmol) in tetrahydrofuran (250 mL) at 0C, and stirred at 0C for 1 hour to form lithium hexamethyldisilazide (LHMDS). A solution of compound 3_60_2 (22.6 g, 107.6 mmol) in tetrahydrofuran (250 mL) was added slowly at 0C, and the mixture was warmed to room temperature slowly and stirred for 16 hours at room temperature. A IN hydrochloric acid solution (300 mL) was added to the reaction mixture to give a precipitate which was collected to give pure compound 3_60_3 (17 g, 70 % yield). From the mother liquor an additional amount of crude compound 3_60_3 (10 g) was obtained as a gum. [00485] NMR (400 MHz, DMSO-d6): delta = 5.32 (s, 2H), 7.32-7.52 (m, 5H), 7.78 (dd, J = 8.8, 2.9 Hz, 1H), 8.25 (d, J = 8.6 Hz, 1H), 8.54 (d, J = 2.7 Hz, 1H), 9.18 (s, 2H), 9.32 (s, 2H).
  • 4
  • [ 78760-60-8 ]
  • [ 1448674-61-0 ]
  • 5
  • [ 78760-60-8 ]
  • [ 1448674-62-1 ]
  • 6
  • [ 78760-60-8 ]
  • [ 1448674-63-2 ]
  • 7
  • [ 78760-60-8 ]
  • [ 75-16-1 ]
  • [ 858597-92-9 ]
YieldReaction ConditionsOperation in experiment
90% In tetrahydrofuran; for 3h;Inert atmosphere; Reflux; To a reflux condenser 20mL round bottom flask was added 5mL anhydrous tetrahydrofuran solution, 0.5mmol <strong>[78760-60-8]5-benzyloxy-2-cyanopyridine</strong>,The mixture was stirred and replaced with nitrogen for three times. 1.5 mmol of methylmagnesium bromide was slowly added under the protection of nitrogen at room temperature. The whole system was heated to reflux and reacted for 3 hours.The whole reaction was poured into ice-water and extracted three times with dichloromethane, each time 20 mL, concentrated to give a white solid product, 102 mg, yield 90%.
  • 8
  • [ 97483-77-7 ]
  • [ 100-51-6 ]
  • [ 78760-60-8 ]
YieldReaction ConditionsOperation in experiment
80.2% With sodium hydride; In N,N-dimethyl-formamide; at 0 - 5℃; for 0.416667h; Step C: at 0 ~ 5 , benzyl alcohol (7.68g, 71.0mmol) was added dropwise 60% sodium hydride (2.84g, 71.0mmol) in DMF (60mL) suspension.After the addition was completed, stirring was continued for 10 minutes, and then 5-bromo-2-cyanopyridine (10.0 g, 54.6 mmol) was added portionwise.The resulting mixture was stirred at this temperature for a further 15 minutes.Add water (180 mL), filter, and filter cake with water (100 mL)5-Benzyloxy-2-cyanopyridine (25) (9.2 g) was obtained. The yield was 80.2%.
  • 9
  • [ 78760-60-8 ]
  • [ 925-90-6 ]
  • 1-[5-(benzyloxy)pyridin-2-yl]propan-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
98.7% In tetrahydrofuran; at -5 - 0℃; for 1h; Step D: at -5 ~ 0 , a 2M ethylmagnesium bromide in THF (26.5mL, 53mmol) was added dropwise to compound 25 (8.6g, 40.9mmol) in THF (30 mL) solution. After the addition was completed, the resulting mixture was further stirred at this temperature for 1 hour. Slowly add water (90mL),Adjust the pH to 3~4 with 2M hydrochloric acid.Extracted with ethyl acetate (100 mL × 3),The combined organic phases were washed with water (50 mL) and brine brineThe solvent was evaporated under reduced pressure to give 1-(5-benzyloxypyridin-2-yl)propan-1-one (26) (9.74 g). The yield was 98.7%.
 

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