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Type | HazMat fee for 500 gram (Estimated) |
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Structure of 230615-59-5
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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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CAS No. : | 230615-59-5 |
Formula : | C13H10F3N3O5 |
M.W : | 345.23 |
SMILES Code : | FC(F)(F)C(N1CC(C2)C3=CC([N+]([O-])=O)=C([N+]([O-])=O)C=C3C2C1)=O |
MDL No. : | MFCD10566032 |
InChI Key : | BDTXJBWOCIFUMR-UHFFFAOYSA-N |
Pubchem ID : | 21864744 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H315-H319-H228 |
Precautionary Statements: | P240-P210-P241-P264-P280-P302+P352-P370+P378-P337+P313-P305+P351+P338-P362+P364-P332+P313 |
Class: | 4.1 |
UN#: | 1325 |
Packing Group: | Ⅱ |
Num. heavy atoms | 24 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.46 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 8.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 81.03 |
TPSA ? Topological Polar Surface Area: Calculated from |
111.95 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.52 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.2 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.36 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.7 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.51 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.25 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.29 |
Solubility | 0.178 mg/ml ; 0.000516 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.19 |
Solubility | 0.0225 mg/ml ; 0.0000653 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.21 |
Solubility | 2.11 mg/ml ; 0.00612 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 |
No |
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) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
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 |
-6.84 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 |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.15 |
* 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 trifluorormethanesulfonic acid; nitric acid; In dichloromethane; at 0 - 15℃;Product distribution / selectivity; | On the other hand, a 500 mL round bottom flask with thermometer, condenser, addition funnel and magnetic stirring was charged with CF3SO3H (25.9 g, 172.5 mmol), CH2Cl2 (110 mL) and cooled to 0-5 0C. At this temperature, fuming nitric acid (5.4 g, 86.25 mmol) was added slowly. To the resulting slurry at 0-5 0C, the solution obtained in the previous step was slowly added, maintaining the temperature < 15 0C. After the addition, the reaction mixture was stirred overnight. The complete dinitration was confirmed by GC. The crude reaction mixture was poured into water (60 mL) an ice (80 g) and stirred. The phases were separated and the aqueous phase was extracted with CH2Cl2 (3 x 50 mL) . The mixture of the organic phases was washed with aqueous saturated NaHCO3, dried over Na2SO4 and volatiles evaporated under vacuum to obtain 11.9 g of a solid that was suspended and stirred for 2 hours in AcOEt (12 mL) and hexanes (24 mL) . The solid was filtered and washed with hexanes to <n="13"/>obtain the compound of formula (III), 9.1g with a purity of 88.9% by GC (9.8% of meta-dimtrocompound impurity) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68.9% | With trifluorormethanesulfonic acid; nitric acid; In dichloromethane; at 0 - 30℃;Product distribution / selectivity; | Example 10Procedure for Preparation of 1-(4,5-Dinitro-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-triene-10-yl)-2,2,2-trifluoro-ethanone (IX); Fuming nitric acid (390.2 g) was added over 25 to 35 minutes at 0 to 5 C. to a solution of tri-fluoro methane sulfonic acid (1.7 kg) in MDC (2.52 l). The mixture was stirred for 10-15 minutes. To this resulting organic layer, <strong>[230615-51-7]1-(10-Aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-triene-10-yl)-2,2,2-trifluoro-ethanone</strong> in MDC was added over 1.0 to 1.5 hours at 0 to 5 C. After completion of addition, the temperature was immediately raised to 25 to 30 C. The reaction mass was stirred at 25 to 30 C. for 2.0 hours. The progress of the reaction was checked by HPLC. The reaction mixture was quenched in DM water (6.5 l) at 0 to 5 C. The layers were separated, and the aqueous layer was extracted with MDC (2×1.26 l). The combined organic layer was washed with DM water (3×3.2 l), and then with an 8 percent aqueous NaHCO3 solution (1×3.2 l) and DM water (1×2.5 l). The organic layer was concentrated to provide crude 1-(4,5-Dinitro-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-triene-10-yl)-2,2,2-trifluoro-ethanone. This was triturated with ethyl acetate (1.30 l) at 55 to 60 C. for 2 hours. The solid was filtered and washed with chilled ethyl acetate (630 ml) to provide pure 1-(4,5-Dinitro-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-triene-10-yl)-2,2,2-trifluoro-ethanone having a yield of 68.9 percent and an HPLC purity of 99.55 percent. |
With trifluorormethanesulfonic acid; nitric acid; In dichloromethane; at 0 - 15℃;Product distribution / selectivity; | A l L round bottom flask with thermometer, condenser, addition funnel and magnetic stirring was charged with CF3SO3H (67.8 g, 452 mmol), CH2Cl2 (280 mL) and cooled to 0-5 0C. At this temperature, fuming nitric acid (14.2 g, 226 mmol) was slowly added. To the resulting slurry at 0-5 0C, the solution obtained in the previous step was slowly added, maintaining the temperature < 15 0C. After the addition, the reaction mixture was stirred overnight. The complete dinitration was confirmed by GC. The crude reaction mixture was poured into water (150 mL) an ice (200 g) and stirred. The phases were separated and the aqueous phase was extracted with CH2Cl2 (100 mL) . The mixture of the organic phases was washed with aqueous saturated NaHCO3 <n="18"/>(2x100 mL) , water (100 mL) , dried over Na2SO4 and volatiles evaporated under vacuum to obtain 30.5 g of a solid with a 83.6% purity by GC (12.5% of meta- dinitrocompound impurity) . 20 g of this solid were crystallized in toluene (100 mL) to obtain the compound of formula (III), 15 g of a pale brown solid with a 98.5 % purity by GC (meta-dinitrocompound impurity not detected) . | |
With sulfuric acid; nitric acid; In dichloromethane; at 0 - 30℃; for 7.0h; | Fuming nitric acid (39 g) was slowly added to a solution concentrated sulfuric acid (126.17 g) in methylene chloride (450 ml) followed by stirring at O0C to generate a white precipitate. This step was followed by drop wise addition of a solution of l-(10-aza- tricyclo[6.3.1.02 7]dodeca-2(7),3,5-trien-10-yl)-2,2,2-trifluoro-ethanone (65 g) in methylene chloride (100 ml) through an addition funnel over 30 minutes. The reaction mixture was stirred for 2 hours 30 minutes at 00C and then stirred for 4 hours at 25-30C. The resulting mass was poured into a vigorously stirred mixture of water (650 ml) at 15-200C. The resulting layers were separated and the aqueous layer was extracted with methylene chloride (I x 325 ml). The organic layers were combined and washed with water (3 x 650 ml) and then dried over sodium sulfate and concentrated to afford a solid. The resulting solid was slurried with methanol (325 ml), filtered and dried to yield 60 g of l-(4,5-dinitro-10-aza- tricyclo[6.3.1.02 7]dodeca-2(7),3,5-trien-10-yl)-2,2,2-trifluoro-ethanone as off-white solid (Purity by HPLC: 99.5%). |
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