Structure of 21724-96-9
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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. : | 21724-96-9 |
Formula : | C10H6BrNO2 |
M.W : | 252.06 |
SMILES Code : | O=C(C(C1=CC=C(Br)C=C1)=C2)NC2=O |
MDL No. : | MFCD19328381 |
InChI Key : | YDIFCLVEBRJPOA-UHFFFAOYSA-N |
Pubchem ID : | 19843468 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 58.85 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.17 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.61 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.63 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.11 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.95 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.48 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.75 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.68 |
Solubility | 0.526 mg/ml ; 0.00209 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.21 |
Solubility | 1.55 mg/ml ; 0.00613 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.94 |
Solubility | 0.0287 mg/ml ; 0.000114 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 |
-6.68 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 |
1.0 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) |
2.12 |
* 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 acetate; copper dichloride; In water; acetone; at 0 - 20℃;pH 3 - 3.5; | Preparation 1: 3-(4-bromophenyl)-1H-pyrrole-2,5-dione (P1) A solution of hydrochloric acid (37percent, 27 ml.) in water (11 ml_) was added to 4-bromo aniline (15 g) at room temperature with vigorous stirring and the formed precipitate was allowed to stir for further 30 minutes. Temperature was reduced to 0 0C and a solution of sodium nitrite (6.60 g) in water (17 ml_) was added dropwise to the stirred suspension. At the end of diazotisation, a clear yellow solution was obtained. Maleimide (16.90 g) in acetone (70 mL) was added dropwise at 0 0C and then the pH of the solution was adjusted to 3-3.5 by adding sodium acetate. Copper (II) chloride (1.76 g) was added to the vigorously stirred mixture. The reaction mixture was allowed to stir at 0 0C for 1 h and overnight at room temperature. Acetone was removed in vacuo, the residue was filtered and dried overnight in vacuo to give the crude title compound (14.12 g) which was used without further purification.MS (mlz): 251 [M-H]". |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Preparation 2: (1/?,5S/1S,5/?)-1-(4-bromophenyl)-3-azabicyclo[3.1.0]hexane-2,4- dione (P2) Milled potassium hydroxide (6.29 g) was added in small portions to a stirred solution of trimethylsulfoxonium iodide (24.66 g) in anhydrous DMSO (224 mL). The resulting mixture was allowed to stir at room temperature for 1.5 h then 3-(4-bromophenyl)-1 H-pyrrole-2,5- dione (P1 , 14.12 g) dissolved in DMSO (90 mL) was then added dropwise and the resulting mixture was allowed to stir at room temperature for 20 minutes. Reaction temperature was brought to 0 °C and aqueous saturated NH4CI (150 mL) was slowly added, followed by Et2O (200 mL). After separation of the two phases, the aqueous layer was repeatedly extracted with Et2O (3 x 100 mL). Combined organic layers were washed with brine and then dried over Na2SO4. Evaporation of the solvent gave the crude title compound (9.61 g) which was used without further purification.MS (mlz): 265.1 [M-H]". |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | A solution of hydrochloric acid (37percent, 13 mL) in water (5.5 mL) was added to 4-bromoaniline (7.48 g, 43.52 mmol) at r.t. with vigorous stirring and the formed precipitate was allowed to stir for 30 min. The reaction mixture was cooled to 0 °C and a solution of sodium nitrite (3.30 g, 47.87 mmol) in water (9 mL) was added dropwise. At the end of diazotization, a clear yellow solution was obtained. Maleimide (8.45 g, 87.05 mmol) in acetone (35 mL) was added dropwise at 0 °C and then the pH of the solution was adjusted to 3-3.5 by adding sodium acetate. CuCl2 (0.88 g, 6.57 mmol) was added to the vigorously stirred mixture. The reaction mixture was stirred at 0 °C for Ih and overnight at r.t. After completion of the reaction as confirmed by TLC, solvents were removed in vacuo to afford the crude compound, which was purified by column chromatography (silica gel, 4: 6 EtOAc: Pet. ether) to afford the title compound as a yellow solid (5.8 g, 57percent). ESIMS (m/z): 252.3 (M+l) | |
57% | Step 1: Preparation of 3-(4-bromophenyl)-1H-pyrrole-2,5-dioneA solution of hydrochloric acid (37percent, 13 mL) in water (5.5 mL) was added to 4-bromoaniline (7.48 g, 43.52 mmol) at r.t. with vigorous stirring and the formed precipitate was allowed to stir for 30 min. The reaction mixture was cooled to 0° C. and a solution of sodium nitrite (3.30 g, 47.87 mmol) in water (9 mL) was added dropwise. At the end of diazotization, a clear yellow solution was obtained. Maleimide (8.45 g, 87.05 mmol) in acetone (35 mL) was added dropwise at 0° C. and then the pH of the solution was adjusted to 3-3.5 by adding sodium acetate. CuCl2 (0.88 g, 6.57 mmol) was added to the vigorously stirred mixture. The reaction mixture was stirred at 0° C. for 1 h and overnight at r.t. After completion of the reaction as confirmed by TLC, solvents were removed in vacuo to afford the crude compound, which was purified by column chromatography (silica gel, 4:6 EtOAc:Pet. ether) to afford the title compound as a yellow solid (5.8 g, 57percent).ESIMS (m/z): 252.3 (M+1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | In toluene; for 18h;Reflux; | To a solution of 3-(4-bromophenyl)-lH-pyrrole-2,5-dione (3.45 g, 13.74 mmol) obtained in Step 1 of Intermediate IX, in toluene (50 mL) was added ethyldiazoacetate (4.27 mL, 41.23 mmol). The reaction mixture was heated to reflux for 18h. After completion of the reaction as confirmed by TLC, solvent was removed in vacuo to afford crude product which was purified by column chromatography (silica gel, 4: 6 EtOAc: Pet. ether) to afford the title compound as a yellow solid (2.66 g, 57percent).ESIMS (m/z): 338.7(M+1) |
57% | In toluene; for 18h;Reflux; | Step 2: Preparation of ethyl 1-(4-bromophenyl)-2,4-dioxo-3-aza-bicyclo[3.1.0]hexane-6-carboxylateTo a solution of <strong>[21724-96-9]3-(4-bromophenyl)-1H-pyrrole-2,5-dione</strong> (3.45 g, 13.74 mmol) obtained in Step 1 of Intermediate IX, in toluene (50 mL) was added ethyldiazoacetate (4.27 mL, 41.23 mmol). The reaction mixture was heated to reflux for 18 h. After completion of the reaction as confirmed by TLC, solvent was removed in vacuo to afford crude product which was purified by column chromatography (silica gel, 4:6 EtOAc:Pet. ether) to afford the title compound as a yellow solid (2.66 g, 57percent).ESIMS (m/z): 338.7 (M+1) |
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