Structure of 937047-04-6
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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. : | 937047-04-6 |
Formula : | C10H12BrN3O2 |
M.W : | 286.13 |
SMILES Code : | O=C(OC(C)(C)C)NN1C(C#N)=CC(Br)=C1 |
MDL No. : | MFCD15142762 |
InChI Key : | SIUZUFSQLYFQRR-UHFFFAOYSA-N |
Pubchem ID : | 57955231 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H312-H332 |
Precautionary Statements: | P280 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.4 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 62.83 |
TPSA ? Topological Polar Surface Area: Calculated from |
67.05 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.73 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.96 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.41 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.48 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.87 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.09 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.45 |
Solubility | 0.102 mg/ml ; 0.000358 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.03 |
Solubility | 0.0267 mg/ml ; 0.0000931 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.67 |
Solubility | 0.616 mg/ml ; 0.00215 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) |
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 |
-5.94 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.98 |
* 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 |
---|---|---|
98% | With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; In acetonitrile; at -30 - 20℃; for 2h; | A IL, 3-neck RB flask was fitted with a mechanical stirrer, nitrogen inlet, thermocouple/JKEM thermocontroller, and a dry-ice acetonitrile cooling. 2-Cyano-pyrrol- l-yl)-carbamic acid, tert-butyl ester (2Og, 96.5 mmol) was added and dissolved in 350 inL acetonitrile. The resulting solution and cooled to below -30 0C. l,3-Dibromo-5,5- dimethylhydantoin (13.79g, 48.26 mmol) was added as a solid, and the reaction was allowed to warm to rt over 2h. Analysis by RP-HPLC at 2h indicated that about 10% starting material remained. The reaction was cooled again to below -30 0C and treated with additional l,3-dibromo-5,5-dimethylhydantoin (1.3 g, 4.8 mmol). The reaction was allowed to warm slowly to rt over 3h. Once RP-HPLC indicated that all starting material had been consumed, the reaction was diluted with 500 mL EtOAc and transferred to a separatory funnel. The organic was washed with IN sodium carbonate, water and brine and then dried with sodium sulfate. Filtration of the organic layer thru silica gel removed much of the colored impurities. Evaporation of the solvent under vacuum provided a reddish oil, which provided orange-brown crystals of the desired product upon seeding (27.16g, 98% yield). This material proved to be only about 90% pure by 1H -NMR. 1H-NMR (DMSO): delta 10.95 (bs, IH), 7.61 (d, IH, J = 2.0 Hz), 7.16 (d, IH, J = 2 Hz), 1.44 (s, 9H, J = 4.4, 1.7 Hz). |
98% | With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; In acetonitrile; at -30 - 20℃; for 5h;Cooling with acetone-dry ice; | A 1 L, 3-neck RB flask was fitted with a mechanical stirrer, nitrogen inlet, thermocouple and thermocontroller, and dry-ice acetonitrile cooling. 2-Cyano-pyrrol-1-yl-carbamic acid, ferf-butyl ester (20 g, 96.5 mmol) was added and dissolved in 350 ml_ acetonitrile and cooled to below -30 0C. 1 ,3-Dibromo-5,5-dimethylhydantoin (13.79 g, 48.26 mmol) was added as a solid, and the reaction was allowed to warm to rt over 2h. Analysis by RP- HPLC at 2h indicated that about 10% starting material remained. The reaction was cooled again to below -30 0C and treated with additional 1 ,3-dibromo-5,5- dimethylhydantoin (1.3 g, 4.8 mmol). The reaction was allowed to warm slowly to rt over 3h. The reaction was diluted with 500 mL EtOAc and transferred to a separatory funnel. The organic layer was washed with 1 N aq sodium carbonate, water and brine and then dried with sodium sulfate. Filtration of the organic layer through silica gel removed much of the colored impurities. Evaporation of the solvent under vacuum provided reddish oil, which provided orange-brown crystals of the desired product upon seeding (27.16 g, 98%). 1H-NMR (DMSO): delta 10.95 (bs, 1 H), 7.61 (d, 1H, J= 2.0 Hz), 7.16 (d, 1H, J= 2 Hz), 1.44 (s, 9H, J= 4.4, 1.7 Hz). MS: LC/MS (+esi), m/z= [M+H]. |
In acetonitrile; at -30 - 20℃;Inert atmosphere; | Example 3 : tert-butyl (4-bromo-2-cyano-lH-pyrrol-l-yl)carbamateUnder an atmosphere of nitrogen, a solution of the compound (27Og) prepared in Example 2 in acetonitrile was added into a flask and was cooled to -3O0C. l,3-Dibromo-5,5- dimethylimidazolidine-2,4-dione (205g) was added into the solution then the bath was removed and the reaction was allowed to warm to room temperature. The solution was added into water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed in saturated sodium chloride aqueous solution, were dried over anhydrous sodium sulfate and solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel (hexane: ethyl acetate = 9:1 - » 5:1) to obtain the title compound (423g) having the following physical data as a yellow oily matter. TLC: Rf 0.44 (hexane : ethyl acetate = 3:1);1HNMR (300 MHz, CDCl3) delta ppm 1.52 (s, 9 H) 6.78 (dd, J=I.8, 0.6 Hz, 1 H) 6.92 (dd, J=I.8, 0.6 Hz, I H) 7.31 (s, l H). |
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