Structure of 6127-19-1
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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. : | 6127-19-1 |
Formula : | C9H8BrN |
M.W : | 210.07 |
SMILES Code : | CC(N1)=CC2=C1C=C(Br)C=C2 |
MDL No. : | MFCD08669941 |
InChI Key : | PTDPLQDPOIVTQW-UHFFFAOYSA-N |
Pubchem ID : | 271554 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.11 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 50.96 |
TPSA ? Topological Polar Surface Area: Calculated from |
15.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.14 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.14 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.24 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.61 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.67 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.96 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.73 |
Solubility | 0.0395 mg/ml ; 0.000188 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.14 |
Solubility | 0.152 mg/ml ; 0.000722 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.53 |
Solubility | 0.00621 mg/ml ; 0.0000296 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) |
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) |
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 |
-5.35 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) |
1.43 |
* 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; PPA; In 5,5-dimethyl-1,3-cyclohexadiene; hexane; dichloromethane; acetone; | PREPARATION 9 4-Bromo-2-methyl-1H-indole and 6-bromo-2-methyl-1H-indole 3-Bromophenylhydrazine hydrochloride (26.5 g) was partitioned between etherand excess 2N sodium hydroxide solution. The ether layer was separated, washed with brine, dried (MgSO4) and evaporated. The residue was redissolved in ether (25 ml) and the solution was cooled in ice. Acetone (25 ml) was added and the mixture was allowed to stand for 20 minutes and then evaporated. The residue was dissolved in acetone (25 ml), the solution was evaporated and the residue azeotroped with xylene. The residue was dissolved in xylene (30 ml) and the solution was added dropwise to stirred polyphosphoric acid (200 g) at 90 C. The mixture was stirred at 100 C. for 4 hours and then cooled and poured into ice water with stirring. The mixture was extracted twice with ether, and the combined extracts were washed with brine and dried (MgSO4). The solvent was evaporated and the residue was chromatographed on silica gel using dichloromethane/hexane (1:4) as eluent. The product fractions were combined and evaporated, and the residue was crystallized twice from hexane to give 6-bromo-2-methyl-1H-indole (8.70 g), m.p. 132-134 C. delta(CDCl3): 2.38(3H,s), 6.15(1H,s), 7.12(1H,dd), 7.32(1H,d), 7.36(1H,d), 7.77(1H,br). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
... falling within the ambit of the formula 1-R8 -pyrrole and carbazole compounds falling within the ambit of the formula 9-R8 -carbazole which are useful in the practice of the processes of this invention for producing the aforesaid methanes and alkanes of Formulas I, XI and XVI. ... 2-Isopropylindole, 1-Methyl-5-bromo-6-nitroindole, 2,5,6-Trimethylindole, 1-Isobutyl-2-methylindole, 6-Bromo-2-methylindole, 1-Hexylindole, 1-(2,5-Dimethylbenzyl)-2-methylindole, 2-Propylindole, ... | ||
The following compounds are exemplary of indoles, pyrroles and carbazoles useful in the practice of this invention. ... 2,5,6-Trimethylindole, 1-Isobutyl-2-methylindole, 6-Bromo-2-methylindole, 1-Hexylindole, ... | ||
The following compounds are exemplary of indoles useful in the practice of this invention. ... 1-Allyl-2-methylindole, 1,2-Dimethyl-6-nitroindole, 1-(4-Chlorobenzyl)-2-methyl-5-nitroindole, 1-Methyl-5-bromo-6-nitroindole, 2,5,6-Trimethylindole, 1-Isobutyl-2-methylindole, 6-Bromo-2-methylindole, 1-Hexylindole, 1-(2,5-Dimethylbenzyl)-2-methylindole, 2-Propylindole, ... |
The following compounds are exemplary of indoles, pyrroles and carbazoles useful in the practice of this invention. ... 2-Isopropylindole, 1-Methyl-5-bromo-6-nitroindole, 2,5,6-Trimethylindole, 1-Isobutyl-2-methylindole, 6-Bromo-2-methylindole, 1-Hexylindole, 1-(2,5-Dimethylbenzyl)-2-methylindole, 2-Propylindole, ... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5%-palladium/activated carbon; In butan-1-ol; at 90℃; for 5h;Product distribution / selectivity; | COMPARATIVE EXAMPLE 4 Synthesis of <strong>[6127-19-1]6-bromo-2-methylindole</strong> In a reaction flask the atmosphere inside of which was substituted by nitrogen, 1.31 g (5.1 mmol) of 4-bromo-2-nitrophenylacetone, 10 g of 1-butanol and 0.065 g of 5% palladium supported on active carbon [manufactured by N.E. CHEMCAT CORPORATION (50% water-containing product)] were placed, hydrogen gas was supplied therein at ordinary pressure and 90 C., and the resulting mixture was reacted for 5 hours. After confirming the disappearance of 4-bromo-2-nitrophenylacetone with liquid chromatography, the atmosphere was substituted by nitrogen, and the catalyst was filtered off through celite. The reaction solution was subjected to quantitative analysis with liquid chromatography, and as a result of it, <strong>[6127-19-1]6-bromo-2-methylindole</strong> was not obtained at all, and a mixture composed of many products including 2-methylindole that bromine atom was eliminated, and the like was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With carbon monoxide;cyclopentadienyl iron(II) dicarbonyl dimer; In toluene; at 120℃; for 5h; | EXAMPLE 11 Synthesis of 6-bromo-2-methylindole In a stainless steel autoclave having an internal volume of 100 mL, 1.31 g (5.1 mmol) of 4-bromo-2-nitrophenylacetone, 72 mg (4 mol %) of cyclopentadienyidicarbonyliron (dimer) and 40 g of toluene were placed under nitrogen atmosphere. After the atmosphere inside of the reactor was substituted by nitrogen gas (10 kgf/cm2) three times, carbon monoxide gas was injected (30 kgf/cm2), and the resulting mixture was reacted at a temperature of 120 C. for 5 hours. After cooling, the reaction solution was subjected to quantitative analysis with liquid chromatography. As a result of it, it was confirmed that 5-fluoro-2-nitrophenylacetone was completely disappeared. The isolation treatment as mentioned above provided 1.00 g (yield 93.0%) of 6-bromo-2-methylindole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With palladium diacetate; copper(II) acetate monohydrate; In dimethyl sulfoxide; at 90℃; for 24h; | Synthesis of 6-Bromo-2-methyl-1H-indole (CXXXIII): A mixture of 3-bromo-aniline (4 g, 0.041 mmol), copper(II) acetate-monohydrate (14.0 g, 0.129 mmol), palladium(II) acetate (0.1 g, 0.000801 mmol) and acetone (100 mL) in dimethylsulfoxide (50 mL) was heated at 90 C for 24 h. The reaction mixture was poured onto cold water and then extracted with ethyl acetate (2 x 250 mL). The organic layer was washed with water and brine, before drying over 10 anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure to afford the crude product, which was purified by column chromatography on (100-200 mesh) silica gel, using 5% ethyl acetate in hexanes, to afford CXXXIII (1.3 mg, 27 %).1H NMR (400 MHz, CDCl3): delta 7.83 (brs, 1H), 7.40 (s, 1H), 7.34 (d, J= 8.3 Hz, 1H), 7.14 (dd, J= 8.5, 1.7 Hz, 1H), 6.17 (s, 1H), 2.41 (s, 3H); MS (ESI, positive mode) m/z 208/210 (MH+, 79/81Br). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | Synthesis of 4-(6-Bromo-2-methyl-indol-1-yl)-benzonitrile (CXXXIV): To a solution of CXXXIII (1.0 g, 4.70 mmol) in 1,4-dioxane (50 mL) was added potassium phosphate (2.98 g, 0.044 mol) and 4-iodo-benzonitrile (2.1 g, 0.010 mol). The mixture was sparged with nitrogen gas for 0.5 h at room temperature. Then copper(I) iodide (0.44 g, 0.230 mmol) and 20 trans-(+/-)-1,2-diaminocyclohexane (0.054 g, 0.470 mmol) were added to the flask. The resultant reaction mixture was heated at 130 C for 48 h. After cooling to room temperature, the reaction mixture was filtered through a bed of celite and the filter pad was washed with ethyl acetate. The filtrate was concentrated under reduced pressure and the remaining crude 197 of 363 {//-- DRAFT --//4069/3020WO/00228726/v2} 4069.3020 WO product mixture was purified by column chromatography on (100-200 mesh) silica gel, using 5% ethyl aceate in hexanes to afford CXXXIV (0.65 g, 44%) as an off-white solid.1H NMR (400 MHz, CDCl3): delta 7.85 (d, J= 8.3 Hz, 2H), 7.4-7.45 (m, 2H), 7.42-7.39 (m, 1H), 7.24-7.22 (m, 2H), 6.41 (s, 1H), 2.29 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With sodium carbonate; In dichloromethane; at 20℃; | General procedure: An appropriate amount 2,3-dichloro-1,4-naphthoquinone 1and the corresponding nucleophile were stirred in dichloromethane (30 mL) with Na2CO3(1.56 g) solution for 2-3 h at room temperature. The color of the solution quickly changedand the reaction was monitored by TLC. Chloroform (30 mL) was added to the reactionmixture. The organic layer was washed with water (4 × 30 mL), and dried over Na2SO4.After the solvent was evaporated the residue was purified by column chromatography onsilica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 105℃; for 14h;Inert atmosphere; | <strong>[6127-19-1]6-bromo-2-methyl-1H-indole</strong> (250 mg, 1.19 mmol), KOAc (410 mg, 4.2 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (520 mg, 2.0 mmol) and PdCl2(dppf)CH2Cl2 (50 mg, 0.061 mmol) were taken up in 1,4-dioxane (7 mL) under Ar. The stirred reaction mixture was heated to 105 C. and stirred for 14 h. The reaction mixture was diluted with water, EtOAc and brine and the phases were separated. The organic phase was dried over Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography (10-60% EtOAc in hexanes) to afford 2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (7.50). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With dmap; In tetrahydrofuran; at 20℃; for 2h; | To a 100 mL round-bottom flask purged with N2 was placed a solution of 6-bromo-2- methyl-1H-indole (1.00 g, 4.76 mmol) and DMAP (58 mg, 0.47 mmol) in THF (15 mL), followed by the addition of Boc2O (1.565 g, 7.17 mmol). The resulting solution was stirred at rt for 2 h then the solvent was removed under reduced pressure. The crude product was purified by column chromatography affording 1.32 g (89%) of the title compound as a yellow solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C14H17BrNO2: 310; found: 310 [M+H]. |
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