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Chemical Structure| 2240-88-2 Chemical Structure| 2240-88-2

Structure of 2240-88-2

Chemical Structure| 2240-88-2

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Product Details of [ 2240-88-2 ]

CAS No. :2240-88-2
Formula : C3H5F3O
M.W : 114.07
SMILES Code : OCCC(F)(F)F
MDL No. :MFCD00190649
InChI Key :HDBGBTNNPRCVND-UHFFFAOYSA-N
Pubchem ID :137512

Safety of [ 2240-88-2 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H315-H319-H335
Precautionary Statements:P210-P280-P301+P330+P331-P302+P352-P304+P312-P305+P351+P338
Class:3
UN#:1993
Packing Group:

Computational Chemistry of [ 2240-88-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 17.89
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.

1.14
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

0.39
Log Po/w (WLOGP)?

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

2.19
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.

0.96
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

1.18
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.17

Water Solubility

Log S (ESOL):?

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

-0.66
Solubility 24.9 mg/ml ; 0.218 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.

-0.38
Solubility 47.5 mg/ml ; 0.416 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

-0.94
Solubility 13.0 mg/ml ; 0.114 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.

-6.72 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

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)

1.0

Application In Synthesis of [ 2240-88-2 ]

* 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 [ 2240-88-2 ]

[ 2240-88-2 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 2240-88-2 ]
  • [ 6608-47-5 ]
  • [ 311-64-8 ]
  • 2
  • [ 2240-88-2 ]
  • [ 928-50-7 ]
  • [ 557-40-4 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; In tetrahydrofuran; 1) 1-Chloropent-4-ene (0.1 mol) and Na2CO3 (11 g) in THF (100 g) are added to 3,3,3-trifluoropropan-1-ol (11 g), the mixture is stirred under reflux for 4 hrs, and the allyl ether is then isolated using conventional laboratory methods.
  • 3
  • [ 311-86-4 ]
  • [ 2240-88-2 ]
YieldReaction ConditionsOperation in experiment
95% With hydrogen; potassium carbonate; In methanol; at 80℃; under 37503.8 Torr; for 3h;Autoclave; 54 g of <strong>[311-86-4]2-bromo-3,3,3-trifluoropropanol</strong>, 79 g of methanol, 9.7 g of activated RaneyNi catalyst and 19.3 g of potassium carbonate were charged into a 300 mL autoclave, stirred, evacuated and replaced with hydrogen After three times, pressure 5Mpa, heated to 80 C, the reaction 3.0h, stop the reaction, cooling, discharge, distillation to 3,3,3 - trifluoropropanol; Yield 95.0%.
  • 4
  • [ 2240-88-2 ]
  • [ 2105-96-6 ]
  • 1-fluoro-2-nitro-4-(3,3,3-trifluoropropoxy)benzene [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; A solution of DIAD (0.743 mL, 3.82 mmol) in THF (2.00 mL) was added slowly to a solution of <strong>[2105-96-6]4-<strong>[2105-96-6]fluoro-3-nitrophenol</strong></strong> (500 mg, 3.18 mmol), 3,3,3-trifluoropropan-l-ol (0.310 mL, 3.50 mmol) and PPli3 (1.00 g, 3.82 mmol) in THF (10.0 mL). The resulting reaction mixture was allowed to stir at RT overnight, after which TLC (20percent EtOAc in Hex) and LC-MS analysis showed product formation. Reaction mixture was concentrated under reduced pressure and residue purified by flash column chromatography: silica gel with a gradient of 5-20percent EtOAc in Hex to afford l-fluoro-2-nitro-4-(3,3,3-trifluoropropoxy)benzene (322 mg, 40.0 percent yield) as a clear golden oil. NMR (400 MHz, DMSO-ifc) d 7.68 (dd, J= 6.0, 3.2 Hz, 1H), 7.54 (dd, J= 10.9, 9.2 Hz, 1H), 7.42 (dt, J = 9.3, 3.5 Hz, 1H), 4.31 (t, .7= 5.9 Hz, 2H), 2.8l (qt, /= 11.4, 5.9 Hz, 2H). 19F NMR (376 MHz, DMSO-ifc) d -63.06 (t, J= 11.2 Hz, 3F), -129.28 (ddd, J= 10.3, 6.0, 3.6 Hz, IF). LCMS RT (Method 2) = 3.491 min.
  • 5
  • [ 2240-88-2 ]
  • [ 1597-32-6 ]
  • 6-(3,3,3-trifluoropropoxy)pyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With sodium hydride; In 1,4-dioxane; at 0 - 90℃; for 2h;Inert atmosphere; A mixture of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (1.00 g, 8.92 mmol) and 3,3,3-trifluoropropan-1-ol (2.03 g, 17.84 mmol) in dioxane (15 mL) was treated with NaH (0.86 g, 35.7 mmol) at 0 C under nitrogen atmosphere and then heated at 90 C for 2 h. The reaction mixture was quenched with cold water and extracted with EtOAc. The organic extract was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude material was purified by flash column chromatography eluting with 10 % to 20 % EtOAc in petroleum ether to provide the title compound (1.30 g, 6.31 mmol, 71 % yield) as a light-yellow oil. 1H NMR (400 MHz, DMSO-d6): d ppm 7.29 (t, J=7.8 Hz, 1 H), 6.01 (dd, J=7.8, 0.7 Hz, 1 H), 5.80 - 5.91 (m, 3 H), 4.34 (t, J=6.2 Hz, 2 H), 2.74 (dtd, J=17.7, 11.6, 6.2 Hz, 2 H). m/z (ESI): 207.2 (M+H)+.
50% With sodium hydride; In 1,4-dioxane; mineral oil; at 0 - 90℃; for 2h;Inert atmosphere; To a solution of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (50 g, 450 mmol, Combi-Blocks) in 1,4-dioxane (500 mL) was added 3,3,3-trifluoropropan-1-ol (102 g, 892 mmol, Apollo) under nitrogen atmosphere and the reaction was cooled to 0 C. NaH (60% in mineral oil, 42.8 g, 1780 mmol) was added to the reaction mixture at 0 C and the resulting mixture was stirred at 90 C for 2 h. The reaction mixture was quenched with cold water (500 mL) and extracted with ethyl acetate (2 x 1000 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography over silica gel (60-120 mesh) using 10% ethyl acetate in hexanes to give the title compound (45 g, 50 % yield) as a pale brown oil. 1H NMR (400 MHz, DMSO-d6): d 7.30- 7.26 (t, J = 7.8 Hz, 1H), 6.02- 6.00 (dd, J = 7.8, 0.8 Hz, 1H), 5.89- 5.86 (m, 3H), 4.36- 4.33 (t, J = 6.2 Hz, 2H), 2.79- 2.67 (qt, J = 11.5, 6.2 Hz, 2H). m/z (ESI): 207.1 (M+H)+.
50% With sodium hydride; In 1,4-dioxane; mineral oil; at 0 - 90℃; for 2h;Inert atmosphere; To a solution of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (50 g, 450 mmol, Combi-Blocks) in 1,4- dioxane (500 mL) was added 3,3,3-trifluoropropan-1-ol (102 g, 892 mmol, Apollo) under nitrogen atmosphere and the reaction was cooled to 0 C. NaH (60% in mineral oil, 42.8 g, 1780 mmol) was added to the reaction mixture at 0 C and the resulting mixture was stirred at 90 C for 2 h. The reaction mixture was quenched with cold water (500 mL) and extracted with ethyl acetate (2 x 1000 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography over silica gel (60-120 mesh) using 10% ethyl acetate in hexanes to give the title compound (45 g, 50 % yield) as a pale brown oil.1H NMR (400 MHz, DMSO-d6): 7.30 - 7.26 (t, J = 7.8 Hz, 1H), 6.02 - 6.00 (dd, J = 7.8, 0.8 Hz, 1H), 5.89 - 5.86 (m, 3H), 4.36 - 4.33 (t, J = 6.2 Hz, 2H), 2.79 - 2.67 (qt, J = 11.5, 6.2 Hz, 2H). m/z (ESI): 207.1 (M+H)+.
50% With sodium hydride; In 1,4-dioxane; mineral oil; at 0 - 90℃; for 2h;Inert atmosphere; To a solution of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (50 g, 450 mmol, Combi-Blocks) in 1,4- dioxane (500 mL) was added 3,3,3-trifluoropropan-1-ol (102 g, 892 mmol, Apollo) under nitrogen atmosphere and the reaction was cooled to 0 C. NaH (60% in mineral oil, 42.8 g, 1780 mmol) was added to the reaction mixture at 0 C and the resulting mixture was stirred at 90 C for 2 h. The reaction mixture was quenched with cold water (500 mL) and extracted with ethyl acetate (2 x 1000 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography over silica gel (60-120 mesh) using 10% ethyl acetate in hexanes to give the title compound (45 g, 50 % yield) as a pale brown oil.1H NMR (400 MHz, DMSO-d6): 7.30 - 7.26 (t, J = 7.8 Hz, 1H), 6.02 - 6.00 (dd, J = 7.8, 0.8 Hz, 1H), 5.89 - 5.86 (m, 3H), 4.36 - 4.33 (t, J = 6.2 Hz, 2H), 2.79 - 2.67 (qt, J = 11.5, 6.2 Hz, 2H). m/z (ESI): 207.1 (M+H)+.

 

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