Structure of 16968-19-7
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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. : | 16968-19-7 |
Formula : | C14H12N2O4 |
M.W : | 272.26 |
SMILES Code : | O=[N+](C1=CC=CC=C1CCC2=CC=CC=C2[N+]([O-])=O)[O-] |
MDL No. : | MFCD00024296 |
InChI Key : | YBOZRPPSBVIHGJ-UHFFFAOYSA-N |
Pubchem ID : | 28168 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 20 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 78.35 |
TPSA ? Topological Polar Surface Area: Calculated from |
91.64 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.22 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.8 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.29 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.8 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.15 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.39 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.04 |
Solubility | 0.0251 mg/ml ; 0.000092 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.42 |
Solubility | 0.00104 mg/ml ; 0.00000381 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.48 |
Solubility | 0.00893 mg/ml ; 0.0000328 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
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 |
-5.26 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.2 |
* 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 |
---|---|---|
95% | Stage #1: With potassium <i>tert</i>-butylate In tetrahydrofuran at 0℃; for 0.0333333 h; Inert atmosphere Stage #2: With bromine In tetrahydrofuran at 20℃; for 0.0833333 h; Inert atmosphere |
Under a nitrogen atmosphere, 2-nitrotoluene (2.00 g, 15.0 mmol) wa sdissolved in dry THF (90 mL), cooled to 0 °C, followed by addition of potassium t-butoxide. The reaction was stirred for 2 min before addition of bromine (3.12 g, 19.5 mmol). After further stirring for 5 min, the reaction was added to 500 mL of ice/water. The precipitate was filtered and the filtrate extracted with CH2Cl2 (3 × 100 mL). The combined organic layers were washed with saturated sodium thiosulfate solution and saturated sodium chloride solution, then dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by crystallization (H2O/EtOH, 1:2) to give 2,2′-dinitrodibenzyl as a white solid (1.94 g, 7.13 mmol, 95percent); mp 121 °C; Rf = 0.33 (n-pentane/CH2Cl2, 1:1). IR (ATR): 2962, 2854, 2343, 1608, 1576, 1509, 1443, 1344, 1310, 1262,1201, 1164, 1126, 1073, 1041, 959, 859, 787, 749, 704, 666, 567, 531, 421 cm–1. 1H NMR (500.1 MHz, CDCl3, 300 K): δ = 7.96 (dd, J = 8.2 Hz, J = 1.2 Hz,2 H, H-3), 7.54 (pseudo t, 2 H, H-5), 7.42 (dd, J = 7.7 Hz, J = 1.3 Hz, 2 H,H-6), 7.38 (pseudo t, 2 H, H-4), 3.25 (s, 4 H, CH2). 13C NMR (125.8 MHz, CDCl3, 300 K): δ = 149.37, 136.01, 133.30,132.49, 127.56, 124.84, 34.44. MS (EI, 70 eV): m/z (percent) = 273 (1) [M + H]+, 255 (8), 237 (9), 178 (21), 136 (100), 120 (70), 92 (85). |
88% | With 5-chloro-1-methyl-1H-pyrazole-4-carbaldehyde; potassium hydroxide In N,N-dimethyl-formamide at 120℃; for 2 h; Inert atmosphere | 3.46 mmol) and 2-nitrotoluene (1.42 g, 10.38 mmol) in DMF(4 mL) was treated with powdered KOH (388 mg, 6.92 mmol) andthen heated at 120 °C for 2 h. The resulting mixture was cooled tor.t. then treated with sat. aq NH4Cl (50 mL) and extracted withEtOAc (3 × 20 mL). The combined organic phases were washedwith brine (1 × 10 mL) and then dried (MgSO4), filtered, and concentratedunder reduced pressure to afford a yellow oil. The residuewas subjected to flash column chromatography (silica gel, EtOAc–hexane, 1:4 → 1:1 gradient elution) to afford two fractions, A and B. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: With iodine; magnesium In tetrahydrofuranHeating Stage #2: With dilithium tetrachlorocuprate In tetrahydrofuran at 55 - 60℃; for 10 h; |
Into a reactor equipped with stirrer, heating device and reflux condenser was added o-nitrobromobenzene (II) (202g, 1.0 mol), tetrahydrofuran (2000g) and iodine (2.02g). After stirring evenly, add in batches polished magnesium chips (28.8g, 1.2 mol), then heat to micro-boiling until the reaction is initiated. then control the heating range. maintaining the reaction mixture at micro-boiling state until the magnesium disappears. The prepared o-nitrobromobenzene Gringard reagent is sealed for later use; In another reactor, add tetrahydrofuran (600g), lithium tetrachlorocuprate (101g) and p-toluenesulfonic acid o-nitrophenethyl ester (III) (321g, 1.0 mol). After stirring evenly, at room temperature add dropwise into the pre-prepared o-nitrobromobenzene Gringard reagent. Dropping temperature not more than 30 °C. After dropping, raise the temperature to 55-60 °C and continously stir the reaction for 10 hours; after the reaction by adding a small amount of dilute hydrochloric acid, filtered to remove insoluble matter, the filtrate is distilled under reduced pressure to remove the majority of the solvent, the obtained residue left standstill and separating solid, to obtain yellow powder, o-dinitrodibenzyl (I) crude, after isopropyl alcohol recrystallization, to obtain light yellow powder, o-dinitrodibenzyl (I) fine powder. 195.8g, yield about 72.0percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | With potassium hydroxide In methanol; water; anhydrous toluene (benzene) | Example 1 Preparation of 2,2'-dinitrobibenzyl A catalytic amount of a metal catalyst (0.01 g metal porfin or 0.005 g metal (AcAc)2 +0.01 g crown-ether) was added to a 33percent methanolic KOH-solution, (34 g KOH in 100 ml methanol). The reaction mixture was cooled to 25° C., 2-nitrotoluene (13.7 g, 0.1 mol) was added and air was passed through the reaction mixture, the temperature of the reaction mixture being kept at 25° C. After 12 hours the passsing through of air was interrupted and 150 ml water and 50 ml methanol was added. The reaction mixture was filtered. The filter layer was dissolved in boiling toluene (benzene), was filtered when hot, was cooled and was filtered again. Recrystallisation from ethanol gave a product with m.p. 120°-121° C. Yield 24-27percent. As a by-product o-nitrobenzoic acid was formed. |
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