Structure of 51686-78-3
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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. : | 51686-78-3 |
Formula : | C6H3Br2NO2 |
M.W : | 280.90 |
SMILES Code : | O=[N+](C1=CC=C(Br)C=C1Br)[O-] |
MDL No. : | MFCD02660416 |
InChI Key : | DXRVYZGVVFZCFP-UHFFFAOYSA-N |
Pubchem ID : | 12315646 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 50.66 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.87 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.21 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.12 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.19 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.06 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.49 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.94 |
Solubility | 0.0321 mg/ml ; 0.000114 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.84 |
Solubility | 0.0402 mg/ml ; 0.000143 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.48 |
Solubility | 0.0932 mg/ml ; 0.000332 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) |
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 |
-5.73 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.05 |
* 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 |
---|---|---|
76% | In ethanol; water; for 2h;Heating / reflux; | To a solution of intermediate 1 (8g, 28.5 mmol) in EtOH (200ml) was added a solution of methylamine 40% in water (200ml) and the mixture was heated under reflux for 2 hours and then cooled. The resulting precipitate was filtered and dried. The title compound was obtained as an orange solid (5g, 76%); m.p. 130-132C. |
76% | In ethanol; water; at 80℃; for 3h; | Step 2: (5-Bromo-2-nitro-phenyl)-methyl-amine; [0310] To a solution of 2,4-dibromo-l-nitro-benzene (2.0 g, 7.14 mmol) in ethanol (50 mL) was added a 40% aqueous solution of methylamine (50 mL). The reaction mixture was stirred at 8O0C in a closed vessel for 3 h, then cooled to O0C. Water was added and the precipitate was filtered, washed with water, and dried in vacuo to give 1.26 g of (5-bromo- 2-nitro-phenyl)-methyl-amine as an orange solid (76% yield): 1H NMR (CDCl3) δ 3.04 (s, 3H), 6.79 (dd, IH), 7.03 (d, IH), 8.05 (d, IH), 8.0-8.1 (broad s, IH); MS (m/z) 231, 233 [M+H+]+. |
76% | In ethanol; water; for 2h;Heating / reflux; | To a solution of intermediate 1 (8g, 28.5 mmol) in EtOH (200ml) was added asolution of methylamine 40% in water (200ml) and the mixture was heated under reflux for 2 hours and then cooled. The resulting precipitate was filtered and dried.The title compound was obtained as an orange solid (5g, 76%); m.p. 130-132C |
68% | In ethanol; water; for 2h;Heating / reflux; | Example 14; 224 229 230 231232Part A:Compound 224 was prepared via the synthetic method described in Example 13 (Part A). A solution of compound 1 (10.0 g, 35.8 mmol) and 40% aqueous methylamine (270 ml_) in ethanol (270 ml_) was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature, resulting in the formation of a precipitate, which was filtered and dried to afford compound 229 as a yellow solid 5.6 g (68%). 1H NMR (400 MHz, DMSO-d6) δ 7.95 (d, 1 H), 7.14 (d, 1 H), 6.79 (dd, 1 H), 2.94 (d, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In DMF (N,N-dimethyl-formamide); at 0 - 70℃; | Step 2:; A mixture of compound 33-2 (6.3 g, 22.4 mmol) and methylamine hydrochloride (3.0 g, 44.8 mmol) in DMF (50 mL) and cooled to 0C. Triethylamine (9.4 mL, 67 mmol) was added and the mixture was allowed to stir at RT for 3.5 h, then heated at 70C overnight. The mixture was poured into water and the resulting precipitate was filtered. The filtrate was extracted with EtOAc (3X) and the extract was washed with water (3X) and saturated NaCI, dried (MgS04), filtered and concentrated to give a mixture of compounds 33-3 and 33-4 as an orange solid (4.8 g), which was used as is in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
STARTING MATERIAL SYNTHESIS EXAMPLE 7 In the same manner as in Starting Material Synthesis Example 4 and using <strong>[7311-95-7]ethyl 2-aminobenzo[b]thiophene-3-carboxylate</strong>, 2,4-dibromonitrobenzene and dimethyl sulfoxide, ethyl 2-(5-bromo-2-nitroanilino)benzo[b]thiophene-3-carboxylate is obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.5% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; toluene; for 2h;Reflux; | 1000 ml of a bottle, with magnetic stirring, adding trimethylene benzene-2-boronic acid (molecular weight: 272, 0.02 mol) 2,48-dibromonitrobenzene (5.28 g (molecular weight: 278, 0.019 mol) Pd (PPh3) 4 used 1.3 g (molecular weight 1154, 0.001265 mol), Sodium carbonate 140 ml (2M), toluene 140 ml, ethanol 140 ml. After argon replacement, reflux, monitoring reaction with TLC, 2 hours after the reaction is complete, cooling, separated from the base layer, evaporated, with 1/10 ethyl acetate / petroleum ether column separation, To give 7.58 g of product having a molecular weight of 427 and a yield of 93.5%. |
43% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; toluene; at 100℃; for 12h; | A 2 L reactor was charged with [Intermediate 1-a] (52 g, 177 mmol) 2-Biphenylboronic acid (42 g, 212 mmol),Tetrakis (triphenylphosphine) palladium (4.1 g, 3.5 mmol),Potassium carbonate (73.4 g, 531 mmol), toluene (600 mL) and distilled water (200 mL) were added, and the mixture was stirred at 100 C for 12 hours.After cooling to room temperature, the organic layer was extracted with ethyl acetate.The organic layer was concentrated under reduced pressure and then separated by column chromatography to obtain [intermediate 1-b]. (41 g, 72%). In Synthesis Example 1- (2) Using 2-triphenylboronic acid instead of [intermediate 1-a]Instead of 2-biphenylboronic acid 2,4-dibromonitrobenzeneSynthesis was carried out in the same way except for using[Intermediate 6-a] was obtained. (38 g, 43%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium hydroxide; cobalt(II) acetate; at 50℃; for 2h;Inert atmosphere; | (1) After mixing 2,4-dibromonitrobenzene with water, heating to 50°C under inert gas protection,Cobalt acetate was added and stirred to mix well, then ammonia was added dropwise to carry out the reflux reaction. After the addition was complete, the reaction was continued for 2 hours while stirring.After completion of the reaction, centrifugation, liquid separation, collection of the organic phase, and distillation under reduced pressure yield a mixture of 3-bromo-4-nitrophenol and 5-bromo-2-nitrophenol.After steam distillation, ether extraction, recrystallization, separation of isomers to obtain 3-bromo-4-nitrophenol In step (1), the molar volume ratio of 2,4-dibromonitrobenzene to water is 0.4 mol/L;The inert gas is helium or argon; the molar ratio of 2,4-dibromonitrobenzene and cobalt acetate is 1.4:1;The molar volume ratio of 2,4-dibromonitrobenzene and ammonia was 0.6 mol/L, and the concentration of ammonia water was 1 mol/L. |