Structure of 3,4-Dibromofuran-2,5-dione
CAS No.: 1122-12-9
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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. : | 1122-12-9 |
Formula : | C4Br2O3 |
M.W : | 255.85 |
SMILES Code : | O=C(C(Br)=C1Br)OC1=O |
MDL No. : | MFCD00030673 |
InChI Key : | GEKJEMDSKURVLI-UHFFFAOYSA-N |
Pubchem ID : | 70727 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 35.98 |
TPSA ? Topological Polar Surface Area: Calculated from |
43.37 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.08 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.68 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.07 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.96 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.0 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.36 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.48 |
Solubility | 0.838 mg/ml ; 0.00328 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.21 |
Solubility | 1.59 mg/ml ; 0.00623 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.19 |
Solubility | 1.67 mg/ml ; 0.00652 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 |
-6.67 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 |
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) |
2.44 |
* 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 |
---|---|---|
87% | With aluminum (III) chloride; bromine; at 120℃; for 16h;Sealed tube; | Synthesis of 3,4-Dibromomaleic anhydride: A mixture of maleic anhydride (2.0 g, 20.39 mmol), aluminum chloride (40.8 mg, 0.3 mmol), and bromine (2.1 ml, 40.78 mmol), was heated at 120 °C for 16 h in sealed tube. After that, it was allowed to coolroom temperature and the reaction mixture was added to ethyl acetate. The ethylacetate solution was filtered and the filtrate was evaporated. To the resulting reddishsolid, 100 nil CHC13 was added and filtered. The filtrate was evaporated to get off-white (yellow) solid in 87percent yield. 13C NMR(CDC13) oe(ppm): 131.8, 159.0. |
83% | With aluminum (III) chloride; bromine; at 160℃; for 20h;Sealed tube; | Under an inert atmosphere, a mixture of maleic anhydride (1.50 g, 15.3 mmol), A1C13 (0.30 g, 0.21 mmol) and Br2 (1.57 mL, 30.6 mmol) was heated at 160 °C in a sealed ampule for 20 h. Upon cooling to room temperature the reaction mixture was carefully opened to air, EtOAc was added the solid filtered off and repeatedly washed with further EtOAc. The filtrate was finally concentrated in vacuo to give the title compound (1) as a yellow solid (3.25 g, 12.8 mmol, 83percent). m.p. 107-110°C; vmax (cm"1) 1769, 1706, 1590; 6C (CDC13, 125 MHz) 164.4 (s), 125.9 (s); HRMS (CI) calculated for C403Br2 [M]+ 253.82087, observed: 253.82082. |
78% | With aluminum (III) chloride; bromine; at 160℃; for 16h;Inert atmosphere; Sealed tube; | Under an inert atmosphere, a solution of maleic anhydride(1.50 g, 15.3 mmol, 1 eq), aluminium trichloride (300 mg,0.21 mmol, cat.) and bromine (4.95 g, 30.6 mmol, 2 eq) was heated at 160° C. in a sealed ampule (note?blast shield) for 16 h. Upon cooling to 21° C. the reaction mixture was stirred for a further 24 h and careffilly opened to ait EtOAc was added and the solid filtered off and repeatedly washed with thrther EtOAc. The filtrate was finally concentrated in vacuo to give the title compound was a yellow solid which was used without thrther purification (3.05 g, 11.9 mmol, 78percent yield).m.p 107-110° C.; ?3CNMR(15OMHz, CD3OD) oe 163.33 (s),125.28 (s); IR (MeOH) 1769, 1706, 1590 cm?; HRMS (CI) calcd for C40313r2 [M]253.82087, 253.82082 observed. |
With aluminum (III) chloride; bromine; at 120℃; for 16h;Sealed tube; | Maleic anhydride (2.0 g, 20 mmol), aluminum(III) chloride (68 mg, 0.51 mmol) and bromine (2.1 mL, 41 mmol) were placed in a sealed reaction vessel and heated to 120 °C for 16 h. After cooling to RT, the reaction was diluted with EtOAc (30 mL) and filtered. The filtrate was then concentrated in vacuo to yield the crude product, 3,4-dibromofuran-2,5-dione, as an orange solid which was used in the next step without further purification. The 3,4-dibromofuran-2,5- dione (1.0 g, 3.9 mmol) was placed in a round-bottomed flask and dissolved in glacial acetic acid (10 mL) at RT. 3.4-Dichloroaniline (0.70 g, 4.3 mmol) was added at RT and then the reaction was heated at reflux for 3 h (120 - 130 °C). The reaction was then cooled to RT and volatiles were removed in vacuo. The crude product was recrystallized from MeOH to yield the title compound as a reddish-brown solid (1.3 g, 80percent). 1H-NMR (400 MHz, DMSO-d6): delta 7.80 (d, J = 8.6 Hz, 1H), 7.69 (d, J = 1.6 Hz, 1H), 7.42 (dd, J = 1.8 Hz, 6.8 Hz, 1H). 13C- NMR (100 MHz, DMSO-d6): delta 162.9, 131.3, 131.2, 131.1 , 129.9, 128.7, 127.3. |
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