Structure of 217959-45-0
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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. : | 217959-45-0 |
Formula : | C5H3F3OS |
M.W : | 168.14 |
SMILES Code : | FC(C1=CC(O)=CS1)(F)F |
MDL No. : | MFCD07779810 |
InChI Key : | JFSLKQBFXHGCHW-UHFFFAOYSA-N |
Pubchem ID : | 11084273 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 31.34 |
TPSA ? Topological Polar Surface Area: Calculated from |
48.47 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.51 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.17 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.62 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.55 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.11 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.39 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.55 |
Solubility | 0.47 mg/ml ; 0.0028 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.82 |
Solubility | 0.254 mg/ml ; 0.00151 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.97 |
Solubility | 1.8 mg/ml ; 0.0107 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) |
No |
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 |
-5.78 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 |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
1.0 alert |
Brenk? Structural Alert: implemented from |
0.0 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) |
2.32 |
* 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 |
---|---|---|
82% | EXAMPLE 9 Preparation of 4-Hydroxy-2-(trifluoromethyl)thiophene STR23 Neat 3-hydroxy-5-trifluoromethyl-2-thiophenecarboxylic acid (180 g, 0.849 mol) is slowly heated under argon to give rapid evolution of gas at 90 C. Heating at 90 C. is continued for an additional 3.5 hours. The resultant oil is vacuum distilled through a 6 inch Vigreaux column packed with 1/4 inch glass cylinders to give the title product as a clear liquid, 118 g (82% yield), bp 70-74 C./4 mm Hg, identified by 1 H-NMR and 13 C-NMR analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With pyridine; In dichloromethane; at 0 - 20℃; for 3.0h; | TRIFLUOROMETHANESULFONIC anhydride (12 ML, 92. 8 mmol, 2 eq. ) was added drop- wise to a 0 C solution of <strong>[217959-45-0]3-hydroxy-5-trifluoromethylthiophene</strong> (7. 8 g, 46.4 mmol, prepared as in Synthesis 2000 get reference), pyridine (7.4 M 1, 9 2. 8 M MOL, 2 eq. ), and DICHLOROMETHANE (230 ML). The mixture was allowed to warm to rt and maintained for 3 h. At this time, the solution was diluted with DICHLOROMETHANE (200 ML), washed with brine (100 ML), 1 M HCI (100 ml), and brine (100 ML). The organic layer was dried (MGS04), filtered, and concentrated to yield 1 as a reddish-orange oil (12. 8 g, 92 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | 3-Hydroxy-5-trifluoromethylthiophen A mixture of 1G (7.75 g) and tetrachloromethane (50 ml) was treated with iodotrimethylsilane (12.30 ml) and heated to 60 C. for 12 hours. The reaction mixture was stirred at room temperature for 12 hours. Water (50 ml) was added and the resulting reaction mixture was extracted with dichloromethane three times. The combined organic phases were washed with water and dried. The crude reaction mixture was eluted through hexane (100 g/silica gel) to remove benzyliodide and then with diethyl ether. The etheral phases were concentrated and distilled in vacuo to give the product (3.33 g, 74%) having a boiling point of 65-66 C. at 4 mm. | |
74% | 2D 3-Hydroxy-5-trifluoromethylthiophen A mixture of 2G (7.75 g) and tetrachloromethane (50 ml) was treated with iodotrimethylsilane (12.30 ml) and heated to 60 C for 12 hours. The reaction mixture was stirred at room temperature for 12 hours. Water (50 ml) was added and the resulting reaction mixture was extracted with dichloromethane three times. The combined organic phases were washed with water and dried. The crude reaction mixture was eluted through hexane (100 g/silica gel) to remove benzyliodide and then with diethyl ether. The etheral phases were concentrated and distilled in vacuo to give the product (3.33 g, 74 %) having a boiling point of 65-66 C at 4 mm. | |
74% | 3-Hydroxy-5-trifluoromethylthiophen A mixture of 5G (7.75 g) and tetrachloromethane (50 ml) was treated with iodotrimethylsilane (12.30 ml) and heated to 60 C for 12 hours. The reaction mixture was stirred at room temperature for 12 hours. Water (50 ml) was added and the resulting reaction mixture was extracted with dichloromethane three times. The combined organic phases were washed with water and dried. The crude reaction mixture was eluted through hexane (100 g/silica gel) to remove benzyliodide and then with diethyl ether. The etheral phases were concentrated and distilled in vacuo to give the product (3.33 g, 74 %) having a boiling point of 65-66 C at 4 mm. |
1.18 g (82%) | 5D 3-Hydroxy-5-trifluoromethylthiophen 5C (1.80 g) was slowly heated under argon. Evolution of gas was observed at 90 C. Heating was continued for additional 3.5 hours at 90 C. The resulting oil was distilled under reduced pressure (boiling point 70-74 C. at 4 mm) to yield 1.18 g (82 %) of compound 5D. | |
1.18 g (82%) | 1D 3-Hydroxy-5-trifluoromethylthiophen 1C (1.80 g) was slowly heated under argon. Evolution of gas was observed at 90 C. Heating was continued for additional 3.5 hours at 90 C. The resulting oil was distilled under reduced pressure (boiling point 70-74 C. at 4 mm) to yield 1.18 g (82%) of compound 1D. | |
1.18 g (82%) | 2D 3-Hydroxy-5-trifluoromethylthiophen 2C (1.80 g) was slowly heated under argon. Evolution of gas was observed at 90 C. Heating was continued for additional 3.5 hours at 90C. The resulting oil was distilled under reduced pressure (boiling point 70-74 C at 4 mm) to yield 1.18 g (82 %) of compound 5D . | |
1.18 g (82%) | 5D 3-Hydroxy-5-trifluoromethylthiophen 5C (1.80 g) was slowly heated under argon. Evolution of gas was observed at 90 C. Heating was continued for additional 3.5 hours at 90C. The resulting oil was distilled under reduced pressure (boiling point 70-74 C at 4 mm) to yield 1.18 g (82 %) of compound 5D . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | With potassium carbonate; In acetonitrile; for 8.0h;Heating / reflux; | 3. Preparation of N-[(5-methyl-4-[5-(trifluoromethyl)-3-thienyl]oxy}pyrimidin-2-yl)methyl]cyclopropanecarboxamide, (Example No. 206 from Table 2); A mixture of 0.2 g (1.23 mmol) of <strong>[217959-45-0]3-hydroxy-5-trifluoromethylthiophene</strong>, 0.33 g (1.23 mmol) of N-[5-methyl-4-(methylsulfonyl)pyrimidin-2-yl]methyl}cyclopropane-carboxamide and 0.34 g (2.45 mmol) of K2CO3 in 20 ml of acetonitrile is stirred under reflux for 8 h and then allowed to stand overnight. The mixture is then poured into 20 ml of water and extracted four times with 20 ml of CH2Cl2. The combined organic phases are dried over Na2SO4 and concentrated. Chromatographic purification on silica gel using EA gives 0.08 g (18%) of product. 1H-NMR: delta [CDCl3] 0.75 (m, 2H), 0.92 (m, 2H), 1.40 (m, 1H), 2.30 (s, 1H), 4.58 (d, 2H), 6.65 (bs, 1H), 7.38 (m, 1H), 7.40 (m, 1H), 8.20 (s, 1H). |
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