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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
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Structure of 705-24-8
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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.
4.5
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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 705-24-8 |
Formula : | C5HCl2F3N2 |
M.W : | 216.98 |
SMILES Code : | ClC1=NC(=NC(=C1)Cl)C(F)(F)F |
MDL No. : | MFCD08436597 |
InChI Key : | QFWVAJQVYBRTCL-UHFFFAOYSA-N |
Pubchem ID : | 15713197 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H301-H314 |
Precautionary Statements: | P280-P301+P310-P305+P351+P338-P310 |
Class: | 8(6.1) |
UN#: | 2922 |
Packing Group: | Ⅱ |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 37.05 |
TPSA ? Topological Polar Surface Area: Calculated from |
25.78 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.97 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.05 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.95 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.92 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.3 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.84 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.41 |
Solubility | 0.0843 mg/ml ; 0.000388 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.26 |
Solubility | 0.12 mg/ml ; 0.000553 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.78 |
Solubility | 0.0362 mg/ml ; 0.000167 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 |
-5.46 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 |
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) |
1.56 |
* 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 N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20.0℃; for 60.0h; | To a suspension of 2-trifluoromethyl-pyrimidine-4, 6-diol (3.25 g) in POC13 (7.89 mL) was added Et3N (5.00 mL). The mixture was stirred at 120C for 3 hr, cooled to ambient temperature, and poured into ice water. The aqueous layer was extracted with CHC13 (three times). The combined organic layer was dried over MgS04, filtrated, and concentrated under reduced pressure to give 4, 6-dichloro-2-trifluoromethyl-pyrimidine. To the solution of the above material (1.00 g) in THF (10 mL) were added iPrzNEt (0.98 mL) and 50% aqueous Me2NH (0.48 mL). The mixture was stirred at ambient temperature for 60 hr. To the solution was added saturated aqueous NaHCO3 and the aqueous layer was extracted with CHCI3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated under reduced pressure, and purified by medium-pressure liquid chromatography (silica gel, 5% to 25% EtOAc in hexane) to give (6-chloro-2- trifluoromethyl-pyrimidin-4-yl)-dimethyl-amine (728 mg). ESI MS m/e 225 M+ ; 1H NMR (300 MHz, CDC13) 8 2.77-3. 61 (m, 6 H), 6.50 (s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.8% | With trichlorophosphate; In water; triethylamine; | EXAMPLE 2 4,6-Dichloro-2-trifluoromethylpyrimidine, Compound V, Step 2 4,6-Dihydroxy-2-trifluoromethylpyrimidine (VI; 540 g; 3.0 M) was stirred with phosphorous oxychloride (1300 mL; 2147 g; 14.0 M) in a 5 L round-bottom flask with mechanical stirrer and triethylamine (607 g; 6.0 M) was added over 1 hr. After the exotherm, the reaction was heated on a stem-bath for 3 hr. The reaction mixture was cooled to 40, and then it was poured with stirring into a mixture of 10 kg ice and 2 kg water. The mixture was extracted with 4*0.5 L methylene chloride. The combined extracts were dried (MgSO4) and filtered. The filtrate was concentrated in vacuo to give the crude compound V. When further purification was desired, the crude V was distilled at 48-50/2 mm using a steam-bath (Lit. b.p. 38/1 mm) to give a colorless liquid. The purified yield was 78.8%. Anal. Calcd. for C5 HCl2 F3 N2: C, 27.68; H, 0.47; N, 12.91. Found: C, 27.45; H, 0.39; N, 12.86. |
With triethylamine; trichlorophosphate; at 120℃; for 3h; | To a suspension of 2-trifluoromethyl-pyrimidine-4, 6-diol (3.25 g) in POC13 (7.89 mL) was added Et3N (5.00 mL). The mixture was stirred at 120C for 3 hr, cooled to ambient temperature, and poured into ice water. The aqueous layer was extracted with CHC13 (three times). The combined organic layer was dried over MgS04, filtrated, and concentrated under reduced pressure to give 4, 6-dichloro-2-trifluoromethyl-pyrimidine. To the solution of the above material (1.00 g) in THF (10 mL) were added iPrzNEt (0.98 mL) and 50% aqueous Me2NH (0.48 mL). The mixture was stirred at ambient temperature for 60 hr. To the solution was added saturated aqueous NaHCO3 and the aqueous layer was extracted with CHCI3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated under reduced pressure, and purified by medium-pressure liquid chromatography (silica gel, 5% to 25% EtOAc in hexane) to give (6-chloro-2- trifluoromethyl-pyrimidin-4-yl)-dimethyl-amine (728 mg). ESI MS m/e 225 M+ ; 1H NMR (300 MHz, CDC13) 8 2.77-3. 61 (m, 6 H), 6.50 (s, 1 H). | |
31.4 g | With triethylamine; trichlorophosphate; at 5 - 105℃; for 4h; | To the reaction flask was added phosphorus oxychloride 144.1 g,Stirring 2-trifluoromethyl-4, 6-dihydroxypyrimidine 36g, stirring,Cooling to 5 ~ 10 C dropping triethylamine 55.4 mL, dropwise warming to 100 ~ 105 C for 4 hours,After the control reaction qualified, the control 0 ~ 5 The reaction solution was added to ice water, after stirring,Then add dichloromethane and stir the layers, add methylene chloride in the aqueous phase to extract, combine the organic phases, wash,Filtration and drying gave the crude product. The crude product was distilled to collect the steamed product, 31.4 g of a colorless liquid,Yield 72.4%, HPLC 99.9%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | To a solution of 1 -methylpiperidin-4-ol (35 mg, 0.30 mmol) in THF (0.5 mL) at 0°C was added 60percent NaH (12 mg, 0.30 mmol). After the mixture was stirred for 20 minutes, a solution of Intermediate 2 (42 mg, 0.10 mmol) in THF (0.5 mL) was added. Then the ice bath was removed, and the reaction mixture was stirred at room temperature for two hours. The reaction was quenched by water (0.1 mL), and concentrated. The residue was purified directly by MS-HPLC to afford Compound 39 (18 mg, 35percent). LCMS (method A): m/z 503.4 (M+H)+. 'H NMR (CDCI3) delta 8.50 (s, 1H), 77.44 (d, 2H), 7.17 (d, 2H), 5.72 (d, 1H), 5.31 (m, 1H), 4.60 (br, 1H), 3.60 (m, 1H), 3.40 (m, 2H), 3.24 (br, 1H), 3.03 (br, 2H), 2.92-2.77 (m, 4H), 2.40 (br, 1H), 2.25 (m, 3H), 2.1 1-1.88 (m,4H); Following procedure as described in Example 2, and replacing THF with DMF, <strong>[50607-30-2]piperidine-2,4-dione</strong> (249 mg, 2.20 mmol) was converted to Compound 3A. The crude material was purified by silica gel chromatography (0-90percent EA/hexane) to afford Compound 3A (375 mg, 64percent). LCMS (method A): m/z 294.3 (M+H)+. XH NMR (CDC13): delta 7.14 (s, 1H), 5.97 (br s, 1H), 5.83 (s, 1H), 3.60 (t, 2H), 2.72 (m, 2H). |
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