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Chemical Structure| 114435-86-8 Chemical Structure| 114435-86-8

Structure of 114435-86-8

Chemical Structure| 114435-86-8

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Product Details of [ 114435-86-8 ]

CAS No. :114435-86-8
Formula : C8H9FO3S
M.W : 204.22
SMILES Code : O=S(C1=CC=C(C)C=C1)(OCF)=O
MDL No. :MFCD20482732
InChI Key :RFCGZPLGJZELOK-UHFFFAOYSA-N
Pubchem ID :13862289

Safety of [ 114435-86-8 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H227-H302-H314-H317
Precautionary Statements:P210-P280-P305+P351+P338-P310
Class:8
UN#:3265
Packing Group:

Computational Chemistry of [ 114435-86-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 45.64
TPSA ?

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

51.75 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.04
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

1.89
Log Po/w (WLOGP)?

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

3.13
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.

1.94
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

1.42
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.08

Water Solubility

Log S (ESOL):?

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

-2.44
Solubility 0.741 mg/ml ; 0.00363 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.

-2.6
Solubility 0.514 mg/ml ; 0.00252 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

-3.14
Solubility 0.148 mg/ml ; 0.000724 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.

-6.2 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

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)

2.17

Application In Synthesis of [ 114435-86-8 ]

* 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 [ 114435-86-8 ]

[ 114435-86-8 ] Synthesis Path-Upstream   1~7

  • 1
  • [ 24124-59-2 ]
  • [ 114435-86-8 ]
YieldReaction ConditionsOperation in experiment
88% With cesium fluoride In tert-Amyl alcohol at 90℃; for 0.25 h; Microwave irradiation; Sealed tube Methylene ditosylate (100 mg, 0.28 mmol) and caesium fluoride (213 mg, 1.4 mmol) were dissolved in tert-amyl alcohol (5 mL) and irradiated in a microwave for 15 minutes at 90 °C. The reaction was allowed to cool and the tert-amyl alcohol was removed under reduced pressure, ice-cold diethyl ether was added and the suspension filtered, then washed with plenty of ice-cold diethyl ether. The filtrate was concentrated under reduced pressure to yield Fluoromethyl 4-methylbenzenesulfonate as a colourless oil (49 mg, 88percent yield). 1H NMR (500 MHz, CDCl3) δ: 2.43 (s, 3H, ArCH3), 5.72 (d, 2H, CH2, J = 51.0 Hz), 7.35 (d, 2H, ArH, J = 8.0 Hz), 7.81 (d, 2H, ArH, J = 8.0 Hz); 13C (125 MHz, CDCl3) δ: 21.67, 98.16 (d, J = 221 Hz), 127.87, 129.96, 133.77, 145.63; 19F (471 MHz, CDCl3) δ: -153.24 (t, J = 50.7 Hz).
41.3% With pentaethylene glycol; cesium fluoride In acetonitrile for 2.5 h; Reflux A stirred solution of methylene bis(tosylate) (2.0 g, 5.61 mmol), hexaethylene glycol(2.11 mL, 8.42 mmol) and cesium fluoride (1.279 g, 8.42 mmol) in acetonitrile(17 mL) was refluxed for 2.5 h. The reaction mixture was diluted with ether, and extracted three times with water to remove hexaethylene glycol. The ether layer was dried over anhydrous sodium sulfate, filtered, and evaporated. The residue was subjected to flash chromatography (4 g silica-gel column, flow rate of 24 ml/min) eluting with100percent hexane for 3 min and increased ethyl acetate from 0percent to 10percent in 20 min togive the product as colorless oil (473 mg, 2.32 mmol, 41.3percent yield).1H NMR (500MHz, CDCl3) δ ppm 7.84 (d, J= 8.0 Hz, 2H), 7.36 (d, J = 8.0 Hz,2H), 5.74 (d, J = 51.0 Hz, 2H), 2.46(s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm 145.92, 134.14, 130.27, 128.22, 98.45 (d, J = -229.5 Hz), 22.01; 19FNMR (470 MHz, CDCl3) δppm 153.2 (t, J = 50.5 Hz).
11% With potassium fluoride; [2.2.2]cryptande In acetonitrile at 110℃; for 1 h; Inert atmosphere Example 3. Preparation of Fluoromethyltosylate (8)C H2OTos2 ^ FCH2OTos7 8 Methylene ditosylate (7) was prepared according to an established literature procedure and analytical data was consistent with reported values (Emmons, W.D., et al. , Journal of the American Chemical Society, 1953; 75:2257; and Neal, T.R., et al. , Journal of Labelled Compounds and Radiopharmaceuticals 2005; 48:557-68).To a solution of methylene ditosylate (7) (0.67 g, 1.89 mmol) in dry acetonitrile (10 mL) was added Kryptofix K222 [4,7,13,16,21,24-hexaoxa-l,10- diazabicyclo[8.8.8]hexacosane] (1.00 g, 2.65 mmol) followed by potassium fluoride (0.16 g, 2.83 mmol). The suspension was then heated to 110°C under nitrogen. After 1 h TLC (7:3 hexane/ethyl acetate/silica/UV254) indicated complete conversion of (7). The reaction mixture was diluted with ethyl acetate (25 mL), washed with water (2 x 15 mL) and dried over MgS04. Chromatography (5--> 10percent ethyl acetate/hexane) gave the desired product (8) as a colorless oil (40 mg, 11percent). ]H NMR (CDC13, 400 MHz) δ 7.86 (d, 2H, / = 8 Hz, aryl CH), 7.39 (d, 2 H, / = 8 Hz, aryl CH), 5.77 (d, 1 H, / = 52 Hz, CH2F), 2.49 (s, 3H, tolyl CH3). 13C NMR (CDC13) δ 145.6 (aryl), 133.8 (aryl), 129.9 (aryl), 127.9 (aryl), 98.1 (d, / = 229 Hz, CH2F), 21.7 (tolyl CH3). HRMS (CI) = 222.0604 (M + NH4)+. Calcd. for C8H13FN03S 222.0600.
11% With potassium fluoride; [2.2.2]cryptande In acetonitrile at 110℃; for 1 h; Inert atmosphere Example 3. Preparation of Fluoromethyltosylate (8)C H2OTos2 ^ FCH2OTos7 8 Methylene ditosylate (7) was prepared according to an established literature procedure and analytical data was consistent with reported values (Emmons, W.D., et al. , Journal of the American Chemical Society, 1953; 75:2257; and Neal, T.R., et al. , Journal of Labelled Compounds and Radiopharmaceuticals 2005; 48:557-68).To a solution of methylene ditosylate (7) (0.67 g, 1.89 mmol) in dry acetonitrile (10 mL) was added Kryptofix K222 [4,7,13,16,21,24-hexaoxa-l,10- diazabicyclo[8.8.8]hexacosane] (1.00 g, 2.65 mmol) followed by potassium fluoride (0.16 g, 2.83 mmol). The suspension was then heated to 110°C under nitrogen. After 1 h TLC (7:3 hexane/ethyl acetate/silica/UV254) indicated complete conversion of (7). The reaction mixture was diluted with ethyl acetate (25 mL), washed with water (2 x 15 mL) and dried over MgS04. Chromatography (5--> 10percent ethyl acetate/hexane) gave the desired product (8) as a colorless oil (40 mg, 11percent). ]H NMR (CDC13, 400 MHz) δ 7.86 (d, 2H, / = 8 Hz, aryl CH), 7.39 (d, 2 H, / = 8 Hz, aryl CH), 5.77 (d, 1 H, / = 52 Hz, CH2F), 2.49 (s, 3H, tolyl CH3). 13C NMR (CDC13) δ 145.6 (aryl), 133.8 (aryl), 129.9 (aryl), 127.9 (aryl), 98.1 (d, J = 229 Hz, CH2F), 21.7 (tolyl CH3). HRMS (CI) = 222.0604 (M + NH4)+. Calcd. for C8H13FN03S 222.0600.
11% With potassium fluoride; [2.2.2]cryptande In acetonitrile at 110℃; for 1 h; Inert atmosphere Example 3. Preparation of Fluoromethyltosylate (8)C H2OTos2 FCH2OTos7 8Methylene ditosylate (7) was prepared according to an established literature procedure and analytical data was consistent with reported values (Emmons, W.D., et al. , Journal of the American Chemical Society, 1953; 75:2257; and Neal, T.R., et al. , Journal of Labelled Compounds and Radiopharmaceuticals 2005; 48:557-68).To a solution of methylene ditosylate (7) (0.67 g, 1.89 mmol) in dry acetonitrile (10 mL) was added Kryptofix K222 [4,7,13,16,21,24-hexaoxa-l,10- diazabicyclo[8.8.8]hexacosane] (1.00 g, 2.65 mmol) followed by potassium fluoride (0.16 g, 2.83 mmol). The suspension was then heated to 110°C under nitrogen. After 1 h TLC (7:3 hexane/ethyl acetate/silica/UV254) indicated complete conversion of (7). The reaction mixture was diluted with ethyl acetate (25 mL), washed with water (2 x 15 mL) and dried over MgS04. Chromatography (5--> 10percent ethyl acetate/hexane) gave the desired product (8) as a colorless oil (40 mg, 11percent). ]H NMR (CDC13, 400 MHz) δ 7.86 (d, 2H, / = 8 Hz, aryl CH), 7.39 (d, 2 H, / = 8 Hz, aryl CH), 5.77 (d, 1 H, / = 52 Hz, CH2F), 2.49 (s, 3H, tolyl CH3). 13C NMR (CDC13) δ 145.6 (aryl), 133.8 (aryl), 129.9 (aryl), 127.9 (aryl), 98.1 (d, / = 229 Hz, CH2F), 21.7 (tolyl CH3). HRMS (CI) = 222.0604 (M + NH4)+. Calcd. for C8H13FN03S 222.0600.

References: [1] Tetrahedron Letters, 2018, vol. 59, # 17, p. 1635 - 1637.
[2] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 18, p. 3956 - 3960.
[3] Journal of Labelled Compounds and Radiopharmaceuticals, 2003, vol. 46, # 6, p. 555 - 566.
[4] ChemMedChem, 2016, vol. 11, # 1, p. 108 - 118.
[5] Patent: WO2012/40133, 2012, A2, . Location in patent: Page/Page column 36-37.
[6] Patent: WO2012/40138, 2012, A2, . Location in patent: Page/Page column 36.
[7] Patent: WO2012/40151, 2012, A2, . Location in patent: Page/Page column 39.
[8] ChemMedChem, 2014, vol. 9, # 7, p. 1476 - 1487.
[9] Journal of Labelled Compounds and Radiopharmaceuticals, 2005, vol. 48, # 8, p. 557 - 568.
[10] Journal of Labelled Compounds and Radiopharmaceuticals, 2013, vol. 56, # 7, p. 360 - 363.
[11] Patent: WO2014/137883, 2014, A1, . Location in patent: Page/Page column 62.
[12] Patent: WO2015/120320, 2015, A1, . Location in patent: Page/Page column 89.
  • 2
  • [ 1280126-09-1 ]
  • [ 104-15-4 ]
  • [ 114435-86-8 ]
References: [1] Angewandte Chemie - International Edition, 2011, vol. 50, # 8, p. 1885 - 1889.
  • 3
  • [ 75-11-6 ]
  • [ 16836-95-6 ]
  • [ 114435-86-8 ]
YieldReaction ConditionsOperation in experiment
28% for 20 h; Reflux Example 8. Synthesis of cold Fluoromethyltosylate (15)i iiCH2I2 CH2OTos2 FCH2OTos13 14 15 Scheme 3 i: Silver p-toluenesulfonate, MeCN, reflux, 20 h;ii: KF, MeCN, reflux, 1 h.According to Scheme 3 above:(a) Synthesis of methylene ditosylate (14)Commercially available diiodomethane (13) (2.67 g, 10 mmol) was reacted with silver tosylate (6.14 g, 22 mmol), using the method of Emmons and Ferris, to give methylene ditosylate (10) (0.99g) in 28percent yield (Emmons, W.D., et ah, "Metathetical Reactions of Silver Salts in Solution. II. The Synthesis of Alkyl Sulfonates", Journal of the American Chemical Society, 1953; 75:225).
References: [1] Patent: WO2012/40151, 2012, A2, . Location in patent: Page/Page column 43.
  • 4
  • [ 104-15-4 ]
  • [ 114435-86-8 ]
References: [1] Angewandte Chemie - International Edition, 2017, vol. 56, # 33, p. 9930 - 9934[2] Angew. Chem., 2017, vol. 129, p. 10062 - 10066,5.
  • 5
  • [ 16836-95-6 ]
  • [ 114435-86-8 ]
References: [1] Patent: WO2012/40133, 2012, A2, .
[2] ChemMedChem, 2014, vol. 9, # 7, p. 1476 - 1487.
[3] Patent: WO2014/137883, 2014, A1, .
[4] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 18, p. 3956 - 3960.
[5] Tetrahedron Letters, 2018, vol. 59, # 17, p. 1635 - 1637.
[6] Patent: WO2012/40138, 2012, A2, .
  • 6
  • [ 24124-59-2 ]
  • [ 455-16-3 ]
  • [ 114435-86-8 ]
References: [1] Tetrahedron Letters, 2018, vol. 59, # 17, p. 1635 - 1637.
  • 7
  • [ 104-15-4 ]
  • [ 114435-86-8 ]
References: [1] ChemMedChem, 2014, vol. 9, # 7, p. 1476 - 1487.
 

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