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Chemical Structure| 14348-75-5 Chemical Structure| 14348-75-5

Structure of 14348-75-5

Chemical Structure| 14348-75-5

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Product Details of [ 14348-75-5 ]

CAS No. :14348-75-5
Formula : C13H6Br2O
M.W : 337.99
SMILES Code : C3=C2C1=C(C=C(Br)C=C1)C(C2=CC(=C3)Br)=O
MDL No. :MFCD00010790
InChI Key :CWGRCRZFJOXQFV-UHFFFAOYSA-N
Pubchem ID :259922

Safety of [ 14348-75-5 ]

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

Computational Chemistry of [ 14348-75-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 70.71
TPSA ?

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

17.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.72
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

4.56
Log Po/w (WLOGP)?

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

4.42
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.

3.91
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

4.95
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.11

Water Solubility

Log S (ESOL):?

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

-5.36
Solubility 0.00146 mg/ml ; 0.00000433 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-4.64
Solubility 0.00771 mg/ml ; 0.0000228 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

-6.75
Solubility 0.0000605 mg/ml ; 0.000000179 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

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

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.

-5.12 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

1.0
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)

2.2

Application In Synthesis of [ 14348-75-5 ]

* 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 [ 14348-75-5 ]

[ 14348-75-5 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 14348-75-5 ]
  • [ 1625-91-8 ]
  • C33H32Br2O [ No CAS ]
  • 3
  • [ 2052-07-5 ]
  • [ 6344-61-2 ]
  • [ 14348-75-5 ]
  • [ 171408-84-7 ]
YieldReaction ConditionsOperation in experiment
11 g (77%) With ammonium chloride; magnesium; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; diethyl ether; acetic acid; c 2,7-Dibromo-9,9'-spirobifluorene A Grignard reagent prepared from 0.72 g (30 mmol) of magnesium turnings and 5.1 ml (30 mmol) of 2-bromobiphenyl in 15 ml of diethyl ether was added dropwise while stirring (in an ultrasonic bath) to a boiling suspension of 10.0 g (29.6 mmol) of 2,7-dibromo-9-fluorenone in 100 ml of dry diethyl ether over a period of 2 hours. After addition was complete, the mixture was boiled for a further 3 hours. After cooling overnight, the precipitate formed was filtered off with suction and washed with cold ether. The magnesium complex which had been filtered off with suction was hydrolyzed in a solution of 15 g of ammonium chloride in 250 ml of ice water. After 1 hour, the 9-(2-biphenylyl)-2,7-dibromo-9-fluorenol formed was filtered off with suction, washed with water and sucked dry. For the ring closure reaction, the dried fluorenol was boiled in 100 ml of glacial acetic acid, after addition of 3 drops of 30 concentrated HCl, for 6 hours. The mixture was allowed to crystallize overnight, the product formed was filtered off with suction and washed with glacial acetic acid and water. Yield: 11 g (77percent) of 2,7-dibromo-9,9'-spirobifluorene. This was purified further by recrystallization from THF. 1H-NMR (CDCl3, ppm): 6.73 (d, J=7.63 Hz, 2 H, H-1',8'); 6.84 (d, J=1.83 Hz, 2 H, H-1,8); 7.15 (td, J=7.63, 1.22 Hz, 2 H, H-2',7'); 7.41 (td, J=7.63, 1.22 Hz, 2 H, H-3',6'); 7.48 (dd, J=8.24, 1.83 Hz, 2 H, H-3,6); 7.67 (d, J=8.24; 2 H; H-4,5); 7.85 (d, J=7.63, 2 H, H-4',5').
11 g (77%) With hydrogenchloride; ammonium chloride; magnesium; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; diethyl ether; acetic acid; Example 1 Synthesis of 2,7-dibromo-9,9'-spirobifluorene A Grignard reagent prepared from 0.72 g (30 mmol) of magnesium turnings and 5.1 ml (30 mmol) of 2-bromobiphenyl in 15 ml of diethyl ether is added dropwise over the course of 2 hours while stirring (in an ultrasonic bath) to a boiling suspension of 10.0 g (29.6 mmol) of 2,7-dibromo-9-fluorenone in 1 00 ml of dry diethyl ether. After addition is complete, the mixture is boiled for a further 3 hours. After cooling overnight, the precipitate formed is filtered off with suction and washed with cold ether. The magnesium complex filtered off is hydrolyzed in a solution of 15 g of ammonium chloride in 250 ml of ice water. After 1 hour, the 9-(2-biphenylyl)-2,7-dibromo-9-fluorenol formed is filtered off with suction, washed with water and sucked dry. For the ring closure reaction, the dried fluorenol is boiled in 100 ml of glacial acetic acid, after addition of 3 drops of concentrated hydrochloric acid, for 6 hours. The mixture is allowed to crystallize overnight, the product formed is filtered off with suction and washed with glacial acetic acid and water. Yield: 11 g (77percent) of 2,7-dibromo-9,9'-spirobifluorene. It can be further purified by recrystallization from THF. 1 H-NMR (CDCl3, ppm): 6.73 (d, J=7.63 Hz, 2H, H-1',8'); 6.84 (d, J=1.83 Hz, 2H, H-1,8); 7.15 (td, J=7.63, 1.22 Hz, 2H, H-2',7'); 7.41 (td, J=7.63, 1.22 Hz, 2H, H-3',6'); 7.48 (dd, J=8.24, 1.83 Hz, 2H, H-3,6); 7.67 (d, J=8.24; 2H; H-4,5); 7.85 (d, J=7.63, 2H, H-4',5').
11 g (77%) With ammonium chloride; magnesium; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; diethyl ether; acetic acid; l) Synthesis of 2,7-dibromo-9,9'-spirobifluorene The Grignard reagent prepared from 0.72 g (30 mmol of magnesium turnings and 5.1 ml (30 mmol) of 2-bromobiphenyl in 15 ml of diethyl ether is added dropwise over a period of 2 hours, while stirring (in an ultrasonic bath), to a boiling suspension of 10.0 g (29.6 mmol) of 2,7 dibromo-9-fluorenone in 100 ml of dry diethyl ether. After the addition is complete, the mixture is boiled for a further 3 hours. After cooling overnight, the precipitated solid is filtered off with suction and washed with cold ether. The magnesium complex filtered off is hydrolyzed in a solution of 15 g of ammonium chloride in 250 ml of ice water. After 1 hour, the 9-(2-biphenylyl)-2,7-dibromo-9-fluorenol formed is filtered off with suction, washed with water and sucked dry. For the ring-closure reaction, the dried fluorenol is boiled in 100 ml of glacial acetic acid for 6 hours, after addition of 3 drops of concentrated HCI. The mixture is allowed to crystallize overnight, the product formed is filtered off with suction and is washed with glacial acetic acid and water. Yield: 11 g (77 percent) of 2,7-dibromo-9,9'-spirobifluorene. It can be further purified by recrystallization from THF. 1H-NMR (CDCl3, ppm): 6.73 (sd, J = 7.63 Hz, 2 H, H-1',8'); 6.84 (d, J = 1.83 Hz, 2 H, H-1,8); 7.15 (td, J = 7.63, 1.22 Hz, 2 H, h-2',7'); 7.41 (td, J = 7.63, 1.22 Hz, 2H, H-3',6'); 7.48 (dd, J = 8.24, 1.83 Hz, 2H, H-3,6); 7.67 (d, J = 8.24 Hz; 2 H; H-4,5); 7.85 (d, J= 7.63, 2H, H-4',5').
  • 5
  • [ 14348-75-5 ]
  • [ 34883-46-0 ]
  • [ 1259293-43-0 ]
  • 6
  • [ 14348-75-5 ]
  • [ 82214-69-5 ]
  • [ 171408-84-7 ]
  • 7
  • [ 902518-11-0 ]
  • [ 14348-75-5 ]
  • 2,7-dibromospiro[fluorene-9,8'-indolo[3,2,1-de]acridine] [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% In a 250 mL two-necked flask, 9- (2-bromophenyl) -9H-carbazole (1.65 g, 5.12 mmol) was dissolved in 50 mL of THF. After cooling to -78 ° C, n-BuLi (2.5 M in hexane, 2.15 mL, 5.38 mmol) was slowly added dropwise. After 2 hours, 2,7-dibromo-9Hfluoren-9-one (1.73 g, 5.12 mmol) was added. After 3 hours, the reaction was terminated with an aqueous solution of NH4Cl, diethyl ether . The water was dried over MgSO4 and the solvent was removed. After precipitation with ethanol, the solid was filtered. The resulting solid was dissolved in acetic acid (50 mL), and a catalytic amount of HCl was added thereto. The mixture was refluxed for 6 hours, cooled to room temperature, filtered, washed with ethanol and dried to obtain 2.11 g (73percent) of a white solid.
  • 8
  • [ 14348-75-5 ]
  • [ 100-58-3 ]
  • [ 583-53-9 ]
  • [ 171408-84-7 ]
YieldReaction ConditionsOperation in experiment
76.2% A solution of 10 mL of o-dibromobenzene (0.1 mmol) in methyl tetrahydrofuran was added dropwise to a solution of 5 mL of phenylmagnesium bromide (0.11 mmol) in methyltetrahydrofuran under argon atmosphere at 80 ° C. Reaction 12 h. The reaction solution was then added dropwise to 10 mL of 2, 7-dibromofluorenone (0.1 mmol) in ether. The mixture was heated to reflux for 2 h, hydrolyzed and filtered. The solid was dissolved in 5 mL of mixed acid (glacial acetic acid and hydrochloric acid) (200-300 mesh silica gel) to give the product 2, 7-dibromo-9, 9 '-spirobifluorene , which was purified by column chromatography on silica gel eluted with a mixed solvent of methylene chloride and n-hexane.36 . 2 mg, yield 76.2percent. The resulting 2, 7-dibromo-9,9-spirobifluorene was reacted with lithium diphenylphosphine (0.15 mmol) in tetrahydrofuran solvent. After refluxing for 12 h, methanol was added to the reaction solution, (200-300 mesh silica gel) to obtain the desired product. 2-Bis (diphenylphosphino) -9, 9-spirobifluorene 35. 9 mg was obtained by the same procedure as that of Example 1, Mg, and the yield was 70.1percent.
  • 9
  • [ 14348-75-5 ]
  • [ 18628-07-4 ]
  • C61H36N4O [ No CAS ]
YieldReaction ConditionsOperation in experiment
98.6% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium t-butanolate; In toluene; for 10h;Inert atmosphere; Reflux; synthetic route:250mL three bottles,In the atmosphere of nitrogen gas,0.01 mol of 2,7-dibromo-9-fluorenone was added,0.025 mol of intermediate G1,0.04 mol of sodium tert-butoxide,1 x 10-4 mol Pd (dppf) Cl2,180 mL of toluene,Heated to reflux for 10 hours,Sampling point plate,Raw material reaction is complete;Natural cooling to room temperature (20 ~ 25 ),filter,The filtrate was collected and evaporated under reduced pressure (-0.09 MPa, 85 C)Column chromatography,Get the target product,HPLC purity 98.6%Yield 68.6%.
 

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