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Structure of 175922-78-8

Chemical Structure| 175922-78-8

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Product Details of [ 175922-78-8 ]

CAS No. :175922-78-8
Formula : C33H48Br2
M.W : 604.54
SMILES Code : CCCCCCCCCCC1(CCCCCCCCCC)C2=C(C3=C1C=C(Br)C=C3)C=CC(Br)=C2
MDL No. :MFCD00971288
InChI Key :RLYANTSRYXOALQ-UHFFFAOYSA-N
Pubchem ID :3661211

Safety of [ 175922-78-8 ]

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

Computational Chemistry of [ 175922-78-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 35
Num. arom. heavy atoms 12
Fraction Csp3 0.64
Num. rotatable bonds 18
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 166.31
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.

7.52
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

15.55
Log Po/w (WLOGP)?

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

12.54
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.

9.18
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

13.07
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

11.57

Water Solubility

Log S (ESOL):?

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

-12.45
Solubility 0.0000000002 mg/ml ; 0.0 mol/l
Class?

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

Insoluble
Log S (Ali)?

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

-15.69
Solubility 0.0 mg/ml ; 2.05e-16 mol/l
Class?

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

Insoluble
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

-14.63
Solubility 0.0 mg/ml ; 0.0 mol/l
Class?

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

Insoluble

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

Yes
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.

1.05 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

2.0
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

1.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

1.0
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

4.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.17

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<3.0
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)

4.59

Application In Synthesis of [ 175922-78-8 ]

* 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.

  • Upstream synthesis route of [ 175922-78-8 ]

[ 175922-78-8 ] Synthesis Path-Upstream   1~4

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  • [ 112-29-8 ]
  • [ 16433-88-8 ]
  • [ 175922-78-8 ]
YieldReaction ConditionsOperation in experiment
92.7% With potassium hydroxide; potassium iodide In dimethyl sulfoxide at 0 - 20℃; for 4 h; EXAMPLE 1
2,7-Dibromo-9,9-didecyifluorene
A mixture of 2,7-dibromofluorene (64.8 g, 0.20 mol potassium iodide (3.0 g, 0.018 mol), finely powdered KOH (56.0 g, 1 mol), and DMSO (150 ML) was mechanically stirred under nitrogen in a three-necked round-bottom flask..
The flask was cooled in an ice water bath before adding four batches of the bromoalkyl (90 ML. 95.94 g, 0.434 mol)..
After each addition, the internal temperature rose sharply..
Once the last aliquot was completed, the reaction was stirred for 4 hours at room temperature before water (200 ML) was added..
The solid was filtered off and dried in a desiccator equipped with P2O5 under vacuum for 16 hours..
The crude product was recrystallized from ethanol to produce 2,7-dibromo-9,9-didecylfluorene as white crystals (m.p. 40-41° C.) in 92.7percent yield..
Mass Spec. m/z 602,604,606 (M+), 461,463,465 (M-C10H21), 382,384 (461-Br). Anal. Calcd for C33H48Br2: C, 65.56percent; H, 8.00percent; Br, 26.44percent. Found: C, 64.99percent; H, 8.21percent; Br, 27.25percent.
92% With tetrabutylammomium bromide; sodium hydroxide In water; dimethyl sulfoxide at 20℃; for 4 h; 2.2.1
2,7-dibromo-9,9-didecylfluorene (1)
1-bromodecane (4.42 g, 20.0 mmol) was added by syringe to a mixture of 2,7-dibromofluorene (2.59 g, 8 mmol), tetrabutyl ammonium bromide (0.02 g, 0.064 mmol) and 2.50 mL of 50percent aqueous sodium hydroxide in dimethyl sulfoxide (50.0 mL).
After stirring at room temperature for 4 h, the mixture was poured into water and extracted three times with dichloromethane.
The solvent was removed under reduced pressure and the precipitate was purified by column chromatography on silica gel (eluent: petroleum ether) to afford 2,7-dibromo-9,9-didecylfluorene as a white powder (4.45 g, Yield 92percent).
1H NMR (500 MHz, CDCl3, δ): 7.51 (d, 2H, J = 8.70 Hz, Ar-H), 7.45 (m, 4H, Ar-H), 1.91 (m, 4H, CH2), 1.13 (m, 28H, CH2), 0.85 (t, 6H, J = 6.95 Hz, CH3), 0.58 (m, 4H, CH2). FT-IR (cm-1, KBr): ν = 2950, 2836 (s; CH), 1638, 1551 (w; Ar). Anal. Calcd. for C33H48Br2: C 65.56, H 8.00; Found: C 64.72, H 7.62.
90.7%
Stage #1: With potassium <i>tert</i>-butylate In tetrahydrofuranInert atmosphere
Stage #2: for 5.5 h; Cooling with liquid nitrogen
To a 2 L three-necked round bottom flask equipped with mechanical stir, nitrogen inlet and outlet, 81.00 g (0.250 mol) 25 2,7-dibromo-9H-fluorence and 500 mL 11 THF were charged. After the 2,7-dibromofluorence was dissolved, 58.9 g (0.525 mol) 26 potassium t-butoxide was added in three batch. The mixture was turned from colorless to dark red immediately, 116.1 g (0.525 mol) of 27 1-bromodecane in 150 mL THF was added drop wise within 3.5 hrs. After addition completed, the mixture was stirred under nitrogen for 2 hrs. Potassium salts was removed through filtration. The filtrate was concentrated under vacuum to give yellow viscous oil. The final product was purified by silica gel chromatography using hexanes as eluent. 137.1 g 28 product was obtained as waxy crystals, 90.7percent isolated yield, m.p. 37.8-39.0° C.
References: [1] Patent: US6730793, 2004, B1, . Location in patent: Page column 3.
[2] Polymer, 2014, vol. 55, # 26, p. 6696 - 6707.
[3] Patent: US2018/273524, 2018, A1, . Location in patent: Paragraph 0041.
[4] Journal of Materials Chemistry C, 2019, vol. 7, # 3, p. 709 - 717.
[5] Molecular Crystals and Liquid Crystals, 2013, vol. 578, # 1, p. 26 - 32.
[6] Journal of Polymer Science, Part A: Polymer Chemistry, 2016, vol. 54, # 17, p. 2774 - 2784.
  • 2
  • [ 123864-01-7 ]
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YieldReaction ConditionsOperation in experiment
82.8% With bromine; iodine In dichloromethane; aluminium A solution of 9,9-di-n-decyl-9H-fluorene (21.33 g, 0.047 mol), iodine (0.12 g, 0.47 mmol), and methylene chloride (170 ml) was stirred magnetically in a single-necked round bottom flask covered with aluminum foil to exclude light.
Elemental bromine (5.18 ml, 0.10 mol) in methylene chloride (20 ml) was pipetted into an addition funnel which was then added dropwise to the reaction mixture over a period of 15 minutes.
Residual bromine solution was rinsed out of the addition funnel into the reaction mixture using 20 ml of additional methylene chloride and the reaction was allowed to stir for 20 hours at room temperature.
An aqueous solution (15percent by weight) of sodium bisulfite (NaHSO3) was then added to the reaction mixture and the resulting two phases allowed to stir for 30 min.
The organic layer was then separated and washed 3 times with an equal volume of water and then dried over anhydrous magnesium sulfate.
The solution was filtered, concentrated and the resulting solid recrystallized from absolute ethanol to yield 2,7-dibromo-9,9-di-n-decyl-9H-fluorene as to white crystals, mp 38.1°-38.4° C. in 82.8percent yield.
Mass Spec. m/z 602, 604, 606 (M+), 461, 463, 465 (M--C10 H21), 382, 384 (461-Br).
Elemental Analysis:
Calculated for C33 H48 Br2: C, 65.56; H, 8.00; Br, 26.44. Found: C, 64.99; H, 8.21; Br, 27.25.
82.8% With bromine; iodine In dichloromethane; aluminium A solution of 9,9-di-n-decyl-9H-fluorene (21.33 g, 0.047 mol), iodine (0.12 9, 0.47 mmol), and methylene chloride (170 ml) was stirred magnetically in a single-necked round bottom flask covered with aluminum foil to exclude light.
Elemental bromine (5.18 ml, 0.10 mol) in methylene chloride (20 ml) was pipetted into an addition funnel which was then added dropwise to the reaction mixture over a period of 15 minutes.
Residual bromine solution was rinsed out of the addition funnel into the reaction mixture using 20 ml of additional methylene chloride and the reaction was allowed to stir for 20 hours at room temperature.
An aqueous solution (15percent by weight) of sodium bisulfite (NaHSO3) was then added to the reaction mixture and the resulting two phases allowed to stir for 30 min.
The organic layer was then separated and washed 3 times with an equal volume of water and then dried over anhydrous magnesium sulfate.
The solution was filtered, concentrated and the resulting solid recrystallized from absolute ethanol to yield 2,7-dibromo 9,9-di-n-decyl-9H-fluorene as white crystals, mp 38.1° C.-38.4° C. in 82.8percent yield.
Mass Spec. m/z 602, 604, 606 (M+), 461, 463, 465 (M-C10 H21), 382, 384 (461-Br).
Elemental Analysis:
Calculated for C33 H48 Br2: C, 65.56; H, 8.00; Br, 26.44. Found: C, 64.99; H, 8.21; Br, 27.25.
References: [1] Patent: US5859251, 1999, A, .
[2] Patent: US5770737, 1998, A, .
  • 3
  • [ 123864-01-7 ]
  • [ 175922-78-8 ]
References: [1] Journal of Materials Chemistry, 1999, vol. 9, # 9, p. 2189 - 2200.
[2] Chemical Communications, 2009, # 7, p. 827 - 829.
  • 4
  • [ 86-73-7 ]
  • [ 175922-78-8 ]
References: [1] Journal of Polymer Science, Part A: Polymer Chemistry, 2016, vol. 54, # 17, p. 2774 - 2784.
 

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