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Structure of 103068-20-8

Chemical Structure| 103068-20-8

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Product Details of [ 103068-20-8 ]

CAS No. :103068-20-8
Formula : C18H13Br
M.W : 309.20
SMILES Code : BrC1=CC(=CC(=C1)C1=CC=CC=C1)C1=CC=CC=C1
MDL No. :MFCD00196170
InChI Key :IOPQERQQZZREDR-UHFFFAOYSA-N
Pubchem ID :10070257

Safety of [ 103068-20-8 ]

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

Computational Chemistry of [ 103068-20-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 18
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 85.01
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.33
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

5.87
Log Po/w (WLOGP)?

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

5.78
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.

5.78
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

5.8
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

5.31

Water Solubility

Log S (ESOL):?

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

-6.02
Solubility 0.000292 mg/ml ; 0.000000946 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-5.64
Solubility 0.000704 mg/ml ; 0.00000228 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

-8.27
Solubility 0.00000167 mg/ml ; 0.0000000054 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

Low
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

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

Yes
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.

-4.02 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

1.0
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

2.0
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)

2.17

Application In Synthesis of [ 103068-20-8 ]

* 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 [ 103068-20-8 ]

[ 103068-20-8 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 103068-20-8 ]
  • [ 73183-34-3 ]
  • [ 1036378-83-2 ]
YieldReaction ConditionsOperation in experiment
91% With potassium acetate; palladium dichloride; In 1,4-dioxane; for 3h;Inert atmosphere; Reflux; In a 2 L reaction flask under nitrogen, 65 g (210.22 mmol) of 1-bromo-3,5-diphenyl,Bis (pinacolato) diboron 64.1 g (252.26 mmol),61.9 g (630.66 mmol) of potassium acetate,7.7 g (10.51 mmol) of palladium (II) dichloride and 650 ml of 1,4-dioxane are added and the temperature is raised.After refluxing for 3 hours, the reaction mixture is filtered through celite, extracted with dichloromethane and distilled water, and then the organic layer is treated with anhydrous magnesium sulfate and concentrated under reduced pressure. After separation and purification by silica gel chromatograph,Recrystallization from dichloromethane and methanol gave 68.3 g (91%) of white solid intermediate compound [6-1].
89.3% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In tetrahydrofuran; at 80℃; for 5h;Inert atmosphere; (1) In a 250 mL three-necked flask, nitrogen gas was added, and 0.02 mol of I-14 was added to dissolve in 100 ml of tetrahydrofuran (THF). (Diphenylphosphine) ferrocene) dichloropalladium (II) and 0.05 mol potassium acetate were added, the mixture was stirred, and the mixed solution of the above reactants was heated to reflux at a reaction temperature of 80 C. for 5 hours; after the reaction was completed, cooled and 100 ml of water were added, and the mixture was filtered and dried in a vacuum oven. The obtained residue was separated and purified through a silica gel column to obtain intermediate E14; the purity by HPLC was 99.4%, and the yield was 89.3%.
89.3% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In tetrahydrofuran; at 80℃; for 5h;Inert atmosphere; (1) In a 250mL three-necked bottle, nitrogen gas is added, 0.02mol of raw material I-14 is dissolved in 100ml of tetrahydrofuran (THF), and then 0.024mol of bis (pinacol) diboron, 0.0002mol of Pd (pddf) 2Cl2 and 0.05mol of potassium acetate were added, the mixture was stirred, and the mixed solution of the above reactants was heated to reflux at a reaction temperature of 80 C for 5 hours; after the reaction was completed, cooled and added 100 ml of water, and the mixture was filtered and dried in a vacuum oven. The obtained solid was dissolved in dichloromethane, and then separated and purified through a silica gel column with a dichloromethane: ethyl acetate = 3: 1 eluent to obtain intermediate E14; HPLC purity was 99.4%, and the yield was 89.3%.
86% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 90℃; Sub 2-II-1 (21.61g, 69.9mmol) obtained in the above synthesis was dissolved in DMF in a round bottom flask, Bis (pinacolato) diboron (19.52g, 76.9mmol), Pd (dppf) Cl2 (1.71g, 2.1 mmol), was added KOAc (20.58g, 209.7mmol) and stirred at 90 C. When the reaction is complete, the DMF was removed by distillation and extracted with water and CH2Cl2. The resulting compound and the organic layer was dried over MgSO4 and concentrated to silicagel column and the product was recrystallized 21.41g (yield: 86%) was obtained.
85% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 150℃; for 10h;Inert atmosphere; Nitrogen environment at the 1-bromo-3 ,5-diphenylbenzene (100 g, 323 mmol) to dimethylforamide (DMF) and then dissolved in 1.0 L, here bis (pinacolato) diboron (98.6 g, 388 mmol) and (1, 1 ' -bis (diphenylphosphine) ferrocene) dichloropalladium (II) (2.64 g, 3.23 mmol), and potassiumacetate (95.1 g, 969 mmol) were placed in 150 10 sigan during heating to reflux was. After the reaction was completed, the reaction solution into water and then filter the mixture, and dried in a vacuum oven. The thus obtained residue by flash column chromatography minutes Li to give the compound I-8 (97.8 g, 85%).
80% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane;Reflux; A 500ml round flask, 5'-Bromo-m-terphenyl 150g (485.11mmol, 1eq), bis(pinacolato)diboron 184.78g (727.66mmol, 1.5eq), Pd(dppf)Cl2 17.7g (put 24.26mmol, 0.05eq), KOAc 190.4g (1940.43mmol, 4eq) was stirred under reflux into a 1,4-dioxane 2L. After the reaction was completed, the mixture was extracted with CH2Cl2/H2O, and CH2Cl2 layer was dried with MgSO4. Silica-gel column purification to give the compound C-1, 138g in 80% yield.
86 g With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; for 3h;Inert atmosphere; Reflux; (258.73 mmol) of 1-bromo-3,5-diphenyl, 78.8 g (310.48 mmol) of bis (pinacolato) diboron and 76.18 g (776.19 mmol) of potassium acetate in a 2 L reaction flask under nitrogen atmosphere,9.47 g (12.94 mmol) of (1,1'-bis (diphenylphosphino) ferrocene) palladidium (II) dichloride is added, 800 ml of 1,4-dioxane is added and the temperature is raised.After refluxing for 3 hours, the reaction mixture is filtered through celite, extracted with dichloromethane / distilled water, treated with anhydrous magnesium sulfate and distilled under reduced pressure. The residue was subjected to silica gel chromatography and recrystallized from dichloromethane and methanol to obtain 86 g (93 wt%) of a white solid intermediate compound [41-1]
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In tetrahydrofuran; at 80℃; for 5h;Inert atmosphere; In a 250 mL three-necked flask, nitrogen gas was added, 0.02 mol of the raw material A-9 was added and dissolved in 100 mL of tetrahydrofuran (THF), and then 0.024 mol of the raw material B,0.0002mol (1,1'-bis (diphenylphosphine) ferrocene) dichloropalladium (II) and 0.05mol potassium acetate were added, the mixture was stirred, and the mixed solution of the above reactants was heated to reflux at a reaction temperature of 80 C 5 hours; at the end of the reaction, cool and add 100 mL of water, and filter the mixture and dry in a vacuum oven. The obtained residue was separated and purified through a silica gel column to obtain intermediate M-9.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 24h;Inert atmosphere; Glovebox; In a nitrogen filled glovebox a mixture of the bromo-m-terphenyl (3.350 g, 10.834 mmol, 1.00 eq), Pd(dppf)Cl2 (0.442 g, 0.5417 mmol, 0.05 eq), B2Pin2 (4.127 g, 16.251 mmol, 1.50 eq), and KOAc (3.190 g, 32.502 mmol, 3.00 eq) in anhydrous deoxygenated 1,4-dioxane (100 mL) was placed in a mantle heated to 100 C., stirred vigorously (1000 rpm) for 24 hrs, removed from the heating mantle, allowed to cool gradually to 23 C., suction filtered through a pad of silica gel, rinsed with CH2Cl2 (4×25 mL), the resulting filtrate solution was concentrated onto celite, and purified via silica gel chromatography; 10% CH2Cl2-100% CH2Cl2 in hexanes to afford the boropinacolate ester as a white solid (3.446 g, 9.672 mmol, 89%). NMR indicated pure product. (0252) 1H NMR (500 MHz, Chloroform-d) δ 8.08 (dt, J=2.7, 1.7 Hz, 2H), 7.95 (p, J=2.0 Hz, 1H), 7.73 (dq, J=7.9, 1.5 Hz, 4H), 7.48 (tt, J=8.0, 1.5 Hz, 4H), 7.39 (ddt, J=8.3, 6.9, 1.3 Hz, 2H), 1.42 (s, 6H), 1.41 (s, 6H). 13C NMR (126 MHz, Chloroform-d) δ 141.15, 141.09, 132.49, 128.91, 128.68, 127.36, 127.31, 83.95, 24.90.

  • 2
  • [ 890042-13-4 ]
  • [ 103068-20-8 ]
  • [ 1115023-64-7 ]
  • 3
  • [ 61676-62-8 ]
  • [ 103068-20-8 ]
  • [ 1036378-83-2 ]
YieldReaction ConditionsOperation in experiment
93% Compound 1 (12.0 g, 38.8 mmol) was added to300 mL of anhydrous THF and stirred at -78 C under a nitrogen atmosphere,then 2M n-BuLi (29.0 mL, 58.1 mmol) was added to thereaction mixture. Next, isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane(11.9 mL, 58.1 mmol) was added to the reaction mixture after30 min. After the reaction was finished, the reaction mixture was extractedwith diethyl ether and water. The organic layer was dried withanhydrous MgSO4 and filtered. The solvent was evaporated. The residuewas re-dissolved in CHCl3 and MeOH was added to the solution.The precipitate was filtered and washed with MeOH to afford a whitesolid (12.9 g, 93%). 1H NMR (300 MHz, CDCl3): δ = 8.03 (s, 2H), 7.90(s, 1H), 7.69 (d, 4H), 7.44(t, 4H), 7.35 (t, 2H), 1.37 (s, 12H); EI + -Mass: 356.
87.5% With n-butyllithium; In tetrahydrofuran; at -78℃; for 2h;Inert atmosphere; Compound 3 (10.0 g, 32.3 mmol) was dissolved in400 mE of an anhydrous tetrahydroffiran solvent under a nitrogen atmosphere. 24.3 mE of a 2M normal butyl lithium solution and 9.9 mE of isopropoxy-4,4,5,5-tetramethyl-1 ,3, 2-dioxaborolane were added thereto at -78 C., and the obtained mixture was stirred for 2 hours. When a reaction was complete, the resultant was extracted with chloroform and distilled water and treated with anhydrous magnesium sulfate. The obtained resulting material was reprecipitated by using chloroform and methanol to obtain 10.1 g of a white solid (a yield of 87.5%).
86.9% With n-butyllithium; In tetrahydrofuran; at -78℃;Enzymatic reaction; Compound 3 (6.0 g, 38.7 mmol) was dissolved in 100 mL of anhydrous THF solution and stirred at -78 C, the 2.0 M n-BuLi (12.4 mL) was added. Then isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4 mL) was added to the reaction mixture. After the reaction was finished, extracted with diethyl ether and water. The organic layer was dried by evaporator. Which product was recrystallized from dichloromethane(CHCl3) and methanol (Yield 86.9%). 1H NMR(300 MHz, CDCl3) δ 7.71 (s, 3H), 7.62 (d, 4H), 7.46 (t, 4H),7.40 (t, 2H), 1.37 (s, 12H).
79.2% With n-butyllithium; In tetrahydrofuran; at -78℃;Inert atmosphere; 1.5 g (4.85 mmol) of Intermediate (2) was placed in a flask, and 100 ml of anhydrous THF was added under nitrogen, followed by stirring.2.91 ml (5.82 mol) of 2M n-BuLi was slowly added while maintaining the temperature at -78 C. At -78 [deg.] C, 3.48 ml of 2-isopropoxy-4,4,5,5-tetramethyl- [l, 3,2] dioxaborolane were added. When the reaction was completed, ethyl acetate (EA) and water were used for extraction.The solvent was evaporated to obtain 1.369 g (yield: 79.2%) of a white solid compound (intermediate (3)) which was a product in the ethyl acetate (EA) layer.

  • 4
  • [ 103068-20-8 ]
  • [ 3974-16-1 ]
  • 4,6-dichloro-2-(3,5-diphenylphenyl)-5-phenylpyrimidine [ No CAS ]
  • 5
  • [ 103068-20-8 ]
  • [ 3974-16-1 ]
  • C68H64N6O4 [ No CAS ]
  • 6
  • [ 103068-20-8 ]
  • [ 439090-73-0 ]
  • C31H21NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 8.0h;Reflux; After the compound of Chemical Formula A (10 g, 31.1 mmol) and 1-bromo-3,5-diphenylbenzene (9.6 g, 31.1 mmol) were suspension stirred in THF (310 ml), K2C03 (8.6 g, 62.3 mmol) dissolved in H20 (100 ml), and then tetrakis (triphenylphosphine) palladium(0) (720 mg, 0.62 mmol) were added thereto, and the result was refluxed for 8 hours. Afier the reaction was complete, the temperature was lowered to room temperature, the water layer was removed, and the organic layer was treated with magnesium sulfate (Mg504) and then filtered. The solution was vacuum concentrated under reduced pressure, and colunm purified with a ratio of THF/Hexane=1/3 to obtain a compound of Chemical Formula 1-4 (10 g, yield: 76%). MS: [M+H]=424
 

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