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Chemical Structure| 76-37-9 Chemical Structure| 76-37-9

Structure of 76-37-9

Chemical Structure| 76-37-9

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Product Details of [ 76-37-9 ]

CAS No. :76-37-9
Formula : C3H4F4O
M.W : 132.06
SMILES Code : OCC(F)(F)C(F)F
MDL No. :MFCD00004676
InChI Key :NBUKAOOFKZFCGD-UHFFFAOYSA-N
Pubchem ID :6441

Safety of [ 76-37-9 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H319-H331
Precautionary Statements:P261-P305+P351+P338-P311
Class:3(6.1)
UN#:1986
Packing Group:

Computational Chemistry of [ 76-37-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 2
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 17.94
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.

0.96
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

1.07
Log Po/w (WLOGP)?

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

2.56
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.

1.16
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

1.5
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.45

Water Solubility

Log S (ESOL):?

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

-1.2
Solubility 8.32 mg/ml ; 0.063 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.09
Solubility 10.8 mg/ml ; 0.082 mol/l
Class?

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

Very 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

-0.89
Solubility 17.1 mg/ml ; 0.129 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.

-6.35 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

3.0
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

1.0 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)

1.0

Application In Synthesis of [ 76-37-9 ]

* 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 [ 76-37-9 ]

[ 76-37-9 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 78385-26-9 ]
  • [ 76-37-9 ]
  • [ 879546-71-1 ]
YieldReaction ConditionsOperation in experiment
With tetrabutylammomium bromide; potassium hydroxide; In water; at 60 - 75℃; for 73h; 3-Methyl-3-(2,2,3,3,-tetrafluoropropoxymethyl)oxetane and 3-methyl-3-(2,2,3,3,4,4,5,5-octafluoropentyloxymethyl)-oxetane are designated 4F and 8F monomers (Fig.1). Their preparation was carried out by nucleophilic substitution using phase transfer catalysis (TBAB) [37-39]. Scheme S1 illustrates the reaction of BrOx with fluorinated alcohols. As a specific example for 4F monomer, BrOx (41.25g, 250mmol), 4F alcohol (46.2g, 350mmol) and TBAB (5g, 0.0125mmol) were heated to 60C in 20mL water. Aqueous KOH (15.8g, 87%) in water (20mL) was added drop wise over 1h. The solution was heated to 75C with stirring for 72h. 4F monomer was extracted with dichloromethane, the solution dried with MgSO4, and the product freed of solvent with a rotovap. GC-MS showed the presence of a small amount of BrOx. Short path distillation gave >99% 4F monomer (b.p. 85C/3.3mmHg). 1H NMR (300MHz, CDCl3, delta: ppm): 6.09-6.06, 5.91-5.88, 5.74-5.70 (-CF2H, 1H, t), 4.48-4.34 (oxetane ring, -CH2-, 4H, d), 3.92-3.91, 3.87-3.87, 3.83-3.82 (-CH2CF2-, 2H, t), 3.63 (-CH2O-, 2H, s), 1.30 (-CH3, 3H, s).
  • 2
  • [ 327056-62-2 ]
  • [ 76-37-9 ]
  • 5-(2,2,3,3-tetrafluoropropoxy)picolinonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
47 g With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 20 - 60℃; for 6.5h;Cooling with ice; To a mixture of <strong>[327056-62-2]2-cyano-5-fluoropyridine</strong> 30 g, 2,2,3,3-tetrafluoro-1-propanol 54 g, and NMP 90 mE was added cesium carbonate 130 g under ice-cooling, and the mixtures were then raised to room temperature, and stirred at room temperature for 1.5 hours. The resulting mixtures were warmed to 60 C. and stirred at 60 C. for additional 5 hours, and to the reaction mixtures was added water, and the mixtures were extracted with MTBE. The resulting organic layers were dried over sodium sulfate, and concentrated under reduced pressure. The resulting residues were recrystallized from isopropanol/hexane solvents to give an intermediate compound 11 represented by the followingformula 47 g. 1H-NMR (CDC13) ö: 8.45 (1H, d), 7.71 (1H, dd),7.33 (1H, dd), 6.04 (1H, tt), 4.49 (2H, t).
47 g With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 20 - 60℃; for 6.5h; 130 g of cesium carbonate was added under ice-cooling to a mixture of 30 g of <strong>[327056-62-2]2-cyano-5-fluoropyridine</strong>, 54 g of 2,2,3,3-tetrafluoro-1-propanol and 90 mL of NMP,And the mixture was stirred at room temperature for 1.5 hours.The resulting mixture was heated to 60 C. and stirred at 60 C. for a further 5 hours. Water was added to the reaction mixture, and the mixture was extracted with MTBE.The obtained organic layer was dried over sodium sulfate and concentrated under reduced pressure.The obtained residue was recrystallized from isopropanol / hexane solvent to obtain 47 g of intermediate 11 represented by the following formula.
 

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