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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
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Structure of 2240-88-2
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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. : | 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 |
GHS Pictogram: |
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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: | Ⅲ |
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 |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.14 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.39 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.19 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.96 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.18 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.17 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.66 |
Solubility | 24.9 mg/ml ; 0.218 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.38 |
Solubility | 47.5 mg/ml ; 0.416 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.94 |
Solubility | 13.0 mg/ml ; 0.114 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 |
-6.72 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 |
3.0 |
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 |
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) |
1.0 |
* 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 |
---|---|---|
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. |
Yield | Reaction Conditions | Operation 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%. |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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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