Structure of 6933-49-9
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 6933-49-9 |
Formula : | C13H11NO |
M.W : | 197.23 |
SMILES Code : | COC1=CC(NC2=C3C=CC=C2)=C3C=C1 |
MDL No. : | MFCD09033506 |
InChI Key : | MDKVPSJRUXOFFV-UHFFFAOYSA-N |
Pubchem ID : | 10797986 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 13 |
Fraction Csp3 | 0.08 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 62.3 |
TPSA ? Topological Polar Surface Area: Calculated from |
25.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.1 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.36 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.33 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.44 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.57 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.96 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.75 |
Solubility | 0.0347 mg/ml ; 0.000176 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.56 |
Solubility | 0.0539 mg/ml ; 0.000273 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.09 |
Solubility | 0.0016 mg/ml ; 0.00000811 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 |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
Yes |
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) |
Yes |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.12 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 |
0.0 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) |
1.38 |
* 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 hydroxide; In water; at 110℃; for 4.75h; | Example 1 l-(2-Methoxy-9H-carbazol-9-yl)-3,3-dimethylbutan-2-oneStep A. 2-Methoxy-9H-carbazole2-?ydroxycarbazole (4.83 g) was suspended in 100 mL water. A solution of 1.11 g NaOH in 100 mL water and 3.83 g dimethyl sulfate were added. The mixture was heated in 110 C oil bath for 2.5 hours. After cooling the reaction mixture was filtered. The collected solid was washed with 100 mL each of water and 0.25 M NaOH solution to give a solid. The filtrate and wash was extracted with 4x50 mL ether. This ether solution was combined with 250 mL ethyl acetate solution of the solid collected and washed with 0.2 N NaOH, water, and saturated brine to give a mixture of product and the starting material. This crude product was treated with 6 mL 5 N NaOH and 4.0 mL dimethyl sulfate in 300 mL water at 110 C for 45 minutes. Then, 12.0 mL 5 N NaOH was added and the resulting mixture stirred for 30 minutes. An additional 2.0 mL dimethyl sulfate was added and the resulting mixture heated for another hour. Repeat this sequence with 4.0 mL 5 N NaOH and 2.0 mL dimethyl sulfate. After cooling the reaction mixture, it was filtered to collect the solid product. It was washed with water and dried to give the crude product. It was purified on SGC using 30-55% EtOAc in hexanes to give the title compound as a yellow solid. 1HNMR (CD3OD, 500 MHz) ? 7.92 (d, 7.8 Hz, IH), 7.89 (d, 8.5 Hz, IH), 7.37 (d, 8.0 Hz, IH), 7.25-7.28 (m, IH), 7.08-7.11 (m, IH), 6.96 (d, 2.3 Hz, IH), 6.77 (dd, 2.3 & 8.7 Hz, IH), 3.87 (s, 3H). LC-MS: 3.31 min. (m/Z = 198.1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With triethyl phosphite; for 16h;Heating / reflux; | Synthesis example 11 2-methoxycarbazole 8.36 g (36.7 mmol) 4'-methoxy-2-nitro-1,1'-biphenyl in 40 ml triethylphosphite is refluxed during 16 hours in argon atmosphere. The mixture was allowed to cool to room temperature, upon which the product precipitates. Filtration and washing with methanol gave 6.67 g (93 %) of a white solid 1H NMR (DMSO-d6): delta11.10 (s, 1H), 8.00 (dd, J=1.5 Hz, J=8 Hz, 1H), 7.8 (d, J=8 Hz, 1H), 7.44 (dd, J=1.5 Hz, J=8 Hz, 1H), 7.30 (dt, J=1.5 Hz, J=8 Hz, 1H), 7.12 (dt, J=1.5 Hz, J=8 Hz, 1H), 6.98 (d, J=1.5 Hz, 1H), 6.78 (dd, J=1.5 Hz, J=8 Hz, 1H), 3.83 (s, 3H). 13C NMR (DMSO-d6): delta 158, 141, 140, 124, 123, 121, 119, 118, 116, 111, 108, 94, 55. mp: 239 C. |
70% | In a 500 mL round-bottom flask was added 4?-methoxy-2-nitro-1,1?-biphenyl (10.3 g, 44.7 mmol) and triethyl phosphite (44.2 mL, 258 mmol). The reaction mixture was heated to reflux at 165 C. in an oil bath under nitrogen for 18 hours. The reaction mixture was cooled to room temperature and 60 mL of 6 N HCl was added dropwise over a period of 30 min. with continuous stirring (exothermic reaction). After the addition, the reaction was heated for 3 hours at 80 C., resulting in the formation of copious precipitate. After cooling to room temperature, water was added (100 mL) and the reaction mixture was neutralized with 50% NaOH (aq.) (60-70 mL, exothermic reaction). The resulting mixture was extracted with 3×250 mL EtOAc and the combined organic layers were washed with brine, dried over Na2SO4, filtered and solvent removed under reduced pressure. To this was added 5-10 mL DCM and the insoluble solid was filtered and washed with hexane to give 6.2 g (70%) of 2-methoxy-9H-carbazole as a light yellow solid. The product was confirmed by GC/MS and NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Example 3 2-Methoxy-9H-carbazole A solution of 1a (14.7 g, 64.1 mmol) in triethyl phosphite (50 mL) was refluxed for 4 h, and then cooled to room temperature. The resulting precipitate was collected by filtration and rinsed with Et2 O. The filtrate was rinsed with 1N HCl (2*250 mL), and the resulting precipitate in the organic extract was collected by filtration and combined with the previously obtained precipitate to furnish a white solid (9.0 g, 71% yield): mp 223-225 C.; ?Cummins, J. A.; Tomlinson, M. L., J. Chem. Soc., 3475-7[(1955)]1 H NMR (DMSO-d6) delta11.11 (s, 1H), 7.97 (d, 1H, J=8.4 Hz), 7.95 (d, 1H, J=8.4 Hz), 7.42 (d, 1H, J=7.8 Hz), 7.27 (t, 1H, J=8.1 Hz), 7.09 (t, 1H, J =7.8 Hz), 6.95 (s, 1H), 6.75 (d, 1H, J=8.4 Hz), 3.82 (s, 3H); 13 C NMR (DMSO-d6) delta158.49, 141.10, 139.72, 124.11, 122.66, 120.89, 119.24, 118.53, 116.17, 110.60, 107.69, 94.43, 55.24. Anal. Calcd for C13 H11 NO.0.1H2 O: C, 78.45; H, 5.67; N, 7.04. Found: C, 78.54; H, 5.87; N, 6.77. | |
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride; In toluene; at 60℃;Schlenk technique; | General procedure: In a 10 mL Schlenk tube,The compound (1-4) (0.2 mmol, 39.5 mg) was added,Grubbs-II catalyst (CAS: 246047-72-3) (2 mol%, 5.3 mg)And toluene (15 mL).The reaction mixture was allowed to react at 60 C,TLC was detected until the reaction was complete. The reaction mixture was washed with saturated sodium bicarbonate (20 mL x 2) and extracted with EA (20 mL x 2). The combined organic phases were washed with saturated NaCl (20 mL x 1). After separation, the mixture was dried over anhydrous magnesium sulfate and the organic solvent was removed under reduced pressure. The purified product was purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 3: 1]White solid, yield: 75%. |