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Structure of 114435-86-8
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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 |
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: | Ⅱ |
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 |
51.75 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.04 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.89 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.13 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.94 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.42 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.08 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.44 |
Solubility | 0.741 mg/ml ; 0.00363 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.6 |
Solubility | 0.514 mg/ml ; 0.00252 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.14 |
Solubility | 0.148 mg/ml ; 0.000724 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.2 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.17 |
* 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.
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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). |
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