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Structure of 121219-03-2

Chemical Structure| 121219-03-2

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Product Citations

Product Citations

Jordan Hobbs ; Calum J. Gibb ; Richard. J. Mandle ;

Abstract: Polar liquid crystals possess three dimensional orientational order coupled with unidirectional electric polarity, yielding fluid ferroelectrics. Such polar phases are generated by rod-like molecules with large electric dipole moments. 2,5-Disubstituted 1,3-dioxane is commonly employed as a polar motif in said systems, and here we show this to suffer from thermal instability as a consequence of equatorial-trans to axial-trans isomerism at elevated temperatures. We utilise isosteric building blocks as potential replacements for the 1,3- dioxane unit, and in doing so we obtain new examples of fluid ferroelectric systems. For binary mixtures of certain composition, we observe the emergence of a new fluid antiferroelectric phase - a finding not observed for either of the parent molecules. Our study also reveals a critical tipping point for the emergence of polar order in otherwise apolar systems. These results hint at the possibility for uncovering new highly ordered polar LC phases and delineate distinct transition mechanisms in orientational and polar ordering.

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Alternative Products

Product Details of [ 121219-03-2 ]

CAS No. :121219-03-2
Formula : C6H4BrFO
M.W : 191.00
SMILES Code : BrC1=C(C=C(C=C1)O)F
MDL No. :MFCD00051907
Boiling Point : No data available
InChI Key :MRQYTJXVULSNIS-UHFFFAOYSA-N
Pubchem ID :2779153

Safety of [ 121219-03-2 ]

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

Computational Chemistry of [ 121219-03-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 36.12
TPSA ?

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

20.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.66
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

2.63
Log Po/w (WLOGP)?

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

2.71
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.

2.67
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

2.48
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.43

Water Solubility

Log S (ESOL):?

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

-3.17
Solubility 0.128 mg/ml ; 0.000669 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.

-2.71
Solubility 0.377 mg/ml ; 0.00197 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

-2.96
Solubility 0.211 mg/ml ; 0.00111 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.

-5.6 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

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)

1.31

Application In Synthesis of [ 121219-03-2 ]

* 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 [ 121219-03-2 ]

[ 121219-03-2 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 1166829-70-4 ]
  • [ 121219-03-2 ]
  • [ 1166829-68-0 ]
YieldReaction ConditionsOperation in experiment
43.5% With potassium carbonate;1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride; In N,N-dimethyl-formamide; at 20 - 100℃; for 4h; Intermediate 43-6: Ethyl 2-f4-f2-fluoro-4-hvdroxyphenyl)cvclohex-3-enyl)acetateA solution of Intermediate 43-7 (18.48 g, 62.82 mmol) in DMF (100 mL) was added to a stirred suspension of 4-bromo-3-fluorophenol (10 g, 52.36 mmol), potassium carbonate (21.71 g, 157.07 mmol) and [l,l-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1.163 g, 1.41 mmol) in DMF (100 mL) at ambient temperature. The resulting suspension was stirred at 80 0C under nitrogen for 2 hours. The reaction was incomplete so the temperature was increased to 100 0C and the reaction mixture was stirred for a further 30 minutes and then further [l,l-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1.163 g, 1.41 mmol) was added and the suspension was stirred at 100 0C for a further 45 minutes and then further [l,l-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (400 mg, 0.487 mmol) was added and the suspension was stirred at 100 0C for a further 45 minutes. The reaction mixture was evaporated to dryness and redissolved in EtOAc (200 mL) and 2M HCl (250 mL) was cautiously added. The aqueous layer was further extracted with EtOAc (3 x 200 mL) and the organic extracts were combined, washed saturated brine (300 mL), dried over MgSO4, filtered and evaporated to afford crude product. The crude <n="133"/>product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford the title compound (6.34 g, 43.5 %) as a pale yellow oil.1H NMR (400 MHz, CDCl3) δ 1.27 (3H, t), 1.41 - 1.50 (IH, m), 1.85 - 1.95 (2H, m), 2.14 - 2.21 (IH, m), 2.32 (2H, d), 2.32 - 2.48 (3H, m), 4.16 (2H, q), 4.98 (IH, s), 5.81 (IH, s), 6.51 - 6.56 (2H, m), 7.05 - 7.09 (IH, m); m/z 277 (M-H)".
  • 2
  • [ 1480-65-5 ]
  • [ 124-38-9 ]
  • [ 121219-03-2 ]
  • [ 1335218-46-6 ]
YieldReaction ConditionsOperation in experiment
Synthesis of Intermediate 7A solution of "-butyllithium (2.7N in heptanes; 165 mL, 445 mmol) in THF (300 mL) was cooled to -78°C and treated with 2,2,6,6-tetramethylpiperidine (77 mL, 456 mmol). The reaction mixture was allowed to stir for 30 minutes. A solution of 5-chloro-2- fluoropyridine (50.0 g, 380 mmol) in THF (200 mL) was added drop wise over 30 minutes. After stirring for an additional 30 minutes, the reaction mixture was quenched by bubbling CO2 through the reaction mixture for 10 minutes. The reaction mixture was allowed to warm to RT, and CO2 was bubbled through for an additional 30 minutes. The reaction mixture was then concentrated under reduced pressure and dissolved in DMF (400 mL). 4-Bromo-3-fluorophenol (72.6 g, 380 mmol) was added, followed by potassium carbonate (68.3 g, 494 mmol). The reaction mixture was heated to 120 °C overnight. The reaction mixture was diluted with EtOAc and washed with 4N HC1. The organic layer was separated, washed with water and dried over MgS04. The solvent was removed under reduced pressure. The crude residue was dissolved in Eaton's Reagent (700 mL, 54.0 g, 380 mmol) and the reaction mixture was heated to 120 °C overnight. The reaction mixture was poured onto a mixture of ice and MeOH. The resulting solid was filtered off and washed with water. The solid was suspended in a mixture of MeOH (100 mL) and cyclopropyl methyl ether (200 mL) and filtered off. The grey solid was washed with hexanes and dried yielding 7-bromo-3-chloro-8-fluoro-5H-chromeno[2,3- b]pyridin-5-one (53.76 g, 164 mmol, 43.0 percent yield) as a ~4:1 mixture of isomers.
  • 3
  • [ 1166829-70-4 ]
  • [ 121219-03-2 ]
  • [ 1166829-64-6 ]
  • [ 1166829-66-8 ]
 

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