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Chemical Structure| 935273-86-2 Chemical Structure| 935273-86-2

Structure of 935273-86-2

Chemical Structure| 935273-86-2

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Product Details of [ 935273-86-2 ]

CAS No. :935273-86-2
Formula : C12H12F2O2
M.W : 226.22
SMILES Code : O=C(C1CC(F)(F)C1)OCC2=CC=CC=C2
MDL No. :MFCD18909480
Boiling Point : No data available
InChI Key :RRSMHVQRSRIXGF-UHFFFAOYSA-N
Pubchem ID :56592986

Safety of [ 935273-86-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 935273-86-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 6
Fraction Csp3 0.42
Num. rotatable bonds 4
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 54.75
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.09
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

2.74
Log Po/w (WLOGP)?

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

3.46
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.

2.74
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

3.26
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.86

Water Solubility

Log S (ESOL):?

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

-2.98
Solubility 0.236 mg/ml ; 0.00104 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.

-2.95
Solubility 0.256 mg/ml ; 0.00113 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

-3.92
Solubility 0.0269 mg/ml ; 0.000119 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

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

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.

-5.73 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

0.0
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)

1.9

Application In Synthesis of [ 935273-86-2 ]

* 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 [ 935273-86-2 ]

[ 935273-86-2 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 198995-91-4 ]
  • [ 935273-86-2 ]
YieldReaction ConditionsOperation in experiment
71% With diethylamino-sulfur trifluoride; In dichloromethane; at 20℃; for 16h;Inert atmosphere; To a solution of benzyl 3- oxocyclobutanecarboxylate (1.23g, 6.03 mmol) in DCM (35 mL) was added DAST (0.8 mL, 6.03 mmol) dropwise under nitrogen. The mixture was stirred at r.t. for 16 h and then diluted with DCM. After washed successively in sequence with saturated sodium bicarbonate, IN aq. hydrochloric acid, and brine, the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography with 93% hexane / EtOAc as eluent to give the desired compound as an oil (1 g, 71% yield). 1H NMR (400 MHz, CDC13): delta 7.47 - 7.27 (m, 5H), 5.16 (s, 2H), 3.09 - 2.95 (m, 1H), 2.90 - 2.60 (m, 4H).
71% With diethylamino-sulfur trifluoride; Step B: Benzyl 3,3-difluorocyclobutanecarboxylate To a solution of <strong>[198995-91-4]benzyl 3-oxocyclobutanecarboxylate</strong> (1.23 g, 6.03 mmol) in DCM (35 mL) was added DAST (0.8 mL, 6.03 mmol) dropwise under nitrogen. The mixture was stirred at r.t. for 16 h and then diluted with DCM. After washed successively in sequence with saturated sodium bicarbonate, 1N aq. hydrochloric acid, and brine, the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography with 93% hexane/EtOAc as eluent to give the desired compound as an oil (1 g, 71% yield). 1H NMR (400 MHz, CDCl3): delta 7.47-7.27 (m, 5H), 5.16 (s, 2H), 3.09-2.95 (m, 1H), 2.90-2.60 (m, 4H).
36.54% With dimethylaminosulphur trifluoride; In dichloromethane; at -60 - 15℃; for 10h; To benzyl 3-oxocyclobutane-carboxylate(1.0 g, 4.9 mmol) in dichloromethane(35 mL), was added dropwise DAST(1.6 g, 9.8 mmol) at -60C. After adding, the reaction mixture was warmed slowly to 15C and stirred for 10 hours. After TLC showed that the reaction was completed, the reaction mixture was cooled to 0C. Saturated sodium bicarbonate solution(10 mL) for quenching reaction, the water phase was extracted with dichloromethane(30 mL*2). The organic phase was combined, washed with saturated salt water(10 mL), dried with anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified through silica gel column chromatography (petroleum ether/ethyl acetate=20:1?10:1) to give benzyl 3,3-difluorocyclobutane carboxylate(450 mg, 36.54% yield) as a colorless oil. MS (ESI) Calcd. for C12H12F2O2 [M+H]+ 227, Found 227.
With ethanol; diethylamino-sulfur trifluoride; In dichloromethane; for 12h; Benzyl 3-oxocyclobutanecarboxylate (2-B) (1.23 g, 6.03 mmol) was dissolved in methylene chloride (35 ml). DAST (8.0 ml, 6.03 mmol) was added under nitrogen, followed by anhydrous ethanol (0.4 ml, 7.23 mmol). The mixture was stirred for 12 hours before it was diluted with methylene chloride, washed successively with saturated sodium bicarbonate, IN aq. hydrochloric acid, and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography with 93% hexane/ethyl acetate as eluent to give <n="25"/>2-C as an oil. lH NMR (500 MHz, CDCI3): delta 2.81-2.93 (4H, m), 3.01- 3.04 (IH, m), 5.20 (2H, s), 7.36- 7.42 (5H, m) ppm.
With diethylamino-sulfur trifluoride; In ethanol; dichloromethane; for 12h; Step B:Benzyl 3-oxocyclobutanecarboxylate (2-B) (1.23 g, 6.03 mmol) was dissolved in methylene chloride (35 ml). DAST (8.0 ml, 6.03 mmol) was added under nitrogen, followed by anhydrous ethanol (0.4 ml, 7.23 mmol). The mixture was stirred for 12 hours before it was diluted with methylene chloride, washed successively with saturated sodium bicarbonate, 1N aq. hydrochloric acid, and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography with 93% hexane/ethyl acetate as eluent to give 2-C as an oil.
With diethylamino-sulfur trifluoride; Step B: Benzyl 3,3-difluorocyclobutanecarboxylate To a solution of <strong>[198995-91-4]benzyl 3-oxocyclobutanecarboxylate</strong> (1.23 g, 6.03 mmol) in DCM (35 mL) was added DAST (0.8 mL, 6.03 mmol) dropwise under nitrogen. The mixture was stirred at room temperature for 16 h and then diluted with DCM. After successive washes with saturated sodium bicarbonate, 1N aq. hydrochloride acid, and brine, the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography with 93% hexane/EtOAc as eluent to give the desired compound as an oil. 1H NMR (400 MHz, CDCl3): delta 7.47-7.27 (m, 5H), 5.16 (s, 2H), 3.09-2.95 (m, 1H), 2.90-2.60 (m, 4H).
With diethylamino-sulfur trifluoride; In dichloromethane; at 20℃; for 16h;Inert atmosphere; Step B: Benzyl 3,3-difluorocyclobutanecarboxylate. To a solution of benzyl 3- oxocyclobutanecarboxylate (1.23g, 6.03 mmol) in DCM (35 mL) was added DAST (0.8 mL, 6.03 mmol) dropwise under nitrogen. The mixture was stirred at room temperature for 16 h and then diluted with DCM. After successive washes with saturated sodium bicarbonate, IN aq. hydrochloride acid, and brine, the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography with 93% hexane / EtOAc as eluent to give the desired compound as an oil. H NMR (400 MHz, CDC13): delta 7.47 - 7.27 (m, 5H), 5.16 (s, 2H), 3.09 - 2.95 (m, 1H), 2.90 - 2.60 (m, 4H).
With diethylamino-sulfur trifluoride; In dichloromethane; at 20℃; for 16h;Inert atmosphere; To a solution of <strong>[198995-91-4]benzyl 3-oxocyclobutanecarboxylate</strong> (1 .23g, 6.03 mmol) in DCM (35 mL) was added DAST (0.8 mL, 6.03 mmol) dropwise under nitrogen. The mixture was stirred at room temperature for 16 hand then diluted with DCM. After successive washes with saturated sodium bicarbonate, iN aq. hydrochloride acid, and brine, the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography with 93% hexane EtOAc as eluent to give the desired compound as an oil. ?H NMR (400 MHz, CDC13): 7.47 -7.27 (m, 511), 5.16 (s, 211), 3.09 -2.95 (m, 111), 2.90 -2.60 (m, 411).
With diethylamino-sulfur trifluoride; In dichloromethane; at 20℃; for 16h;Inert atmosphere; Step B: Benzyl 3, 3-difluorocyclobutanecarboxylate. To a solution of benzyl 3- oxocyclobutanecarboxylate (1 .23g, 6.03 mmol) in DCM (35 mL) was added DAST (0.8 mL, 6.03 mmol) dropwise under nitrogen. The mixture was stirred at room temperature for 16 h and then diluted with DCM . After successive washes with saturated sodium bicarbonate, IN aq. hydrochloride acid, and brine, the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product waspurifiedby silica gel chromatography with 93% hexane / EtOAc as eluent to give the desired compound as an oiL H NMR (400MHz, CDC13): delta 7.47 - 7.27 (m, 5H), 5.16 (s, 2H), 3.09 - 2.95 (m, 1H), 2.90 - 2.60 (m, 4H).

 

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