Structure of 99586-31-9
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CAS No. : | 99586-31-9 |
Formula : | C13H8BrNO |
M.W : | 274.11 |
SMILES Code : | BrC1=CC(C2=NC3=CC=CC=C3O2)=CC=C1 |
MDL No. : | MFCD01565105 |
InChI Key : | KHEXVASQRAJENK-UHFFFAOYSA-N |
Pubchem ID : | 870520 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 15 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 67.15 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.03 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.36 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.26 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.47 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.1 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.84 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.91 |
Solubility | 0.00334 mg/ml ; 0.0000122 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.62 |
Solubility | 0.00654 mg/ml ; 0.0000239 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.28 |
Solubility | 0.000143 mg/ml ; 0.000000522 mol/l |
Class? Solubility class: Log S scale |
Poorly 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 |
-4.88 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.55 |
* 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 |
---|---|---|
96% | With Amino glucose-functionalized silica-coated NiFe2O4 nanoparticles; at 20℃; for 0.133333h; | General procedure: A mixture of aldehyde 1 (1.0 mmol), 1,2-aminophenol (1 mmol)and 0.05 g of NiFe2O4(at)SiO2(at)aminoglucose were stirred at roomtemperature under solvent free condition for the required reactiontime according to Table 6 and 7 After completion of the reaction, asindicated by TLC (TLC Silica gel 60 F, ethyl acetate: n-hexane 1: 4),the resulting mixture was diluted with hot ethanol (10 mL) and thecatalyst separated by the external magnet and washed with hotdistilledwater (5 mL) and ethanol (3 mL) two times. The filtratewascooled down to room temperature and the precipitated crudeproduct was recrystallized from ethanol if necessary. |
92% | With oxygen; potassium carbonate; at 80℃; for 6h; | General procedure: In a 25 mL round bottomed flask, a mixture of 2-aminophenol,2-aminothiol (1.2 mmol), aldehyde (1 mmol),K2CO3(1.5 mmol), and MNPs-phenanthroline-Pd catalyst(25 mg) was stirred in PEG (3 ml) at 80 C for 6 h. Theprogress of the reaction was monitored by thin-layer chromatography(TLC). After completion of the reaction, catalystwas separated by an external magnet and the reactionmixture was extracted with H2Oand ethyl acetate and driedover anhydrous Na2SO4.After evaporation of the solvent,the desired product was isolated by silica gel flash columnchromatography with a mixture of petroleum ether/ethylacetate as eluent. |
90% | With dodeca-tungstophosphoric acid; In neat (no solvent); at 20℃;Green chemistry; | General procedure: To a mixture of aromatic aldehyde/s(0.01mol) and 2-aminophenol/substituted 2aminophenol(0.01mol)solid phosphotungesticacid (0.020 g) was added and the whole reactionmixture was blended thoroughly in pestle and mortarwhich subsequently was allowed to grind vigorously with thehelp of mortar for appropriate time(15-25min) at room temperature.The progress of the reaction was monitored by TLC(eluent phase = n-hexane: EtOAc= 1:9). After the completionof the reaction, ethyl acetate was added to this reactionmixture in the pestle to dissolve the organic compound PTAcatalyst was precipitated out. The whole solution was filteredand solvent was removed on rotator evaporator under reducedpressure. The benzoxazole crude product was separatedand purified through the column chromatography usingn-hexane/ethyl acetate (1:9) as an eluent system |
83% | With cerium(IV) oxide; In water monomer; at 30℃; for 0.416667h; | General procedure: A mixture of 2-aminothiophenol (1mmol) and benzaldehyde (1 mmol) was stirred in presence of Nano CeO2(5 mol %) in water at room temperature for 20 minutes. After completion, thereaction mixture was diluted with ethyl acetate and subsequently centrifuged to get the catalyst. Further the reactionmixture was extracted with ethyl acetate (10 x 3mL) and dried over Na2SO4. The solvent was evaporated under reducedpressure to obtain product. The crude product was purified on silica gel columnby using pet ether and ethyl acetate as solvent to get the pure product |
72% | With silica chloride; In neat (no solvent); at 120℃; for 4h; | General procedure: To the flask containing a mixture of substituted benzaldehyde (1mmole) and 2-aminophenol (1mmole) was added silica chloride(1 eq) and was heated on a sand bath at 120 C, TLC was taken afterevery 1 h. After 4 h, TLC showed appearance of new spot. The productwas isolated by first separating out the catalyst by filtration using organicsolvent; the organic layer was dried using anhydrous sodiumsulfate and evaporated under vacuum. The solid thus obtained was recrystallized using petroleum ether and its % yield and melting pointswere determined. The results are tabulated in Table 1 and Table 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With caesium carbonate;copper(l) iodide; 1,10-Phenanthroline; In 1,4-dioxane; at 120℃; for 24h;Inert atmosphere;Product distribution / selectivity; | A mixture of 3-bromobenzoyl chloride (6.005 g, 27.36 mmol), 2-bromoaniline (4.707 g, 27.36 mmol), Cs2CO3 (17.83 g, 54.73 mmol), CuI (0.261 g, 1.37 mmol), 1,10-phenanthroline (0.493 g, 2.74 mmol) and anhydrous 1,4-dioxane (50 mL) was degassed with argon at 40 C. for 30 min while stirring. The reaction mixture was then maintained under argon at 120 C. while stirring until TLC (SiO2, 4:1 hexanes-ethyl acetate) confirmed consumption of the starting material (24 h). Upon cooling to RT, the mixture was filtered and the filtrant washed copiously with ethyl acetate (ca. 350 mL). The filtrate was then washed with sat. NaHCO3, H2O and brine, dried over MgSO4, filter and concentrated in vacuo. Purification of the crude product via flash chromatography (SiO2, 4:1-hexanes:ethyl acetate) afforded 2-(3-bromophenyl)benzo[d]oxazole (7.50 g, 100%) as an off-white solid. |
76% | With caesium carbonate;copper(l) iodide; 1,10-Phenanthroline; In 1,4-dioxane; at 120℃; for 8h; | A mixture of 3-bromobenzoyl chloride (10.0 g, 45.6 mmol), 2-bromoaniline (7.91 g, 46 mmol), Cs2CO3 (30 g, 92 mmol), CuI (0.437 g, 2.3 mmol) and 1,10-phenathroline (0.829 g, 4.6 mmol) in anhydrous 1,4-dioxane (110 mL) was heated at 120 C. for 8 h. After the mixture was cooled to room temperature, it was poured into ethyl acetate (300 mL) and worked up with water (250 mL). The aqueous solution was extracted with dichloromethane (300 mL). The organic phase was collected and combined, dried over Na2SO4. Purification by a short silica gel column (hexanes/ethyl acetate 3:1) gave a solid which was washed with hexanes to give a light yellow solid (5) (9.54 g, 76% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 95℃;Inert atmosphere; | A mixture of 1,3,5-tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene (4) (1.824 g, 4.0 mmol), <strong>[99586-31-9]2-(3-bromophenyl)benzo[d]oxazole</strong> (5) (3.28 g, 12 mmol), Pd(PPh3)4 (0.74 g, 0.64 mmol) and K2CO3 (3.31 g, 24 mmol) in 1,4-dioxane (100 mL) and water (20 mL) was degassed then heated at 95 C. under argon overnight. After cooled to room temperature, filtration and washing with methanol gave a white solid (ET-2) (2.62 g, quantitative yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With N-Bromosuccinimide; {(Pd{Fe(η5-C5H5)(η5-C5H3C(CH3)=NPh)}(μ-Cl))2}; acetic acid; at 100℃; for 8h; | General procedure: Substrate (0.5 mmol), brominating reagent (0.75 mmol) and palladacycle I (1 mol %) were dissolved in AcOH (2 mL) in a 10 ml vial under air and heated at a specific temperature for 8 h. After the reaction was complete, the mixture was diluted with CH2Cl2 (10 mL), filtered through a pad of Celite, and washed multiple times with CH2Cl2. The combined organic solutions were evaporated under reduced pressure and the residue was purified by flash chromatography on silica gel (ethyl acetate/hexane) to give the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.6% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90℃; for 12h; | 20.0 g of the intermediate 21 (72.96 mmol), 20.4 g of bis(pinacolato)diboron (80.26 mmol), 2.98 g of Pd(dppf)Cl2.CH2Cl2 (3.65 mmol), 14.3 g of potassium acetate (145.92 mmol) and 730 ml of dioxane were put into a 1-neck round flask and reacted under reflux at 90 C. for 12 hours. The resultant compound was purified by silica gel column chromatography to obtain 20.5 g of white solid compound (intermediate 22) (yield: 87.6%). |
77% | With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 100℃; for 21h;Inert atmosphere;Product distribution / selectivity; | A mixture of <strong>[99586-31-9]2-(3-bromophenyl)benzo[d]oxazole</strong> (7.500 g, 27.36 mmol), bis(pinacolato)diboron (7.296 g, 28.73 mmol), [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium (1.001 g, 1.368 mmol), potassium acetate (6.176 g, 62.93 mmol) and anhydrous 1,4-dioxane (71 mL) was degassed with argon at 40 C. for 37 min while stirring. The reaction mixture was then maintained under argon at 100 C. while stirring until TLC (SiO2, 2:1 hexanes-dichloromethane) confirmed consumption of the starting material (21 h). Upon cooling to RT, the mixture was filtered and the filtrate washed copiously with ethyl acetate (ca. 700 mL). The filtrate was then washed with sat. NaHCO3, H2O and brine, dried over MgSO4, filter and concentrated in vacuo. Purification of the crude product via flash chromatography (SiO2, 9:1-dichloromethane:hexanes to 19:1-dichloromethane:acetone) afforded 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzo[d]oxazole (6.76 g, 77%) as an off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With copper(l) iodide; C37H51ClFeNPPd; cesium fluoride; In N,N-dimethyl-formamide; at 80℃; for 12h;Inert atmosphere; | General procedure: Aryl halide (0.5 mmol), base (1 mmol), CuI (20 mol %), alkylstannylpyridine(0.75 mmol), and catalyst (1 mol %) were dissolvedin DMF (2 mL) in a 10 mL vial and heated at a specific temperatureunder N2 for 12 h. After the reaction was complete, and thenquenched with water. The mixture was diluted with ethyl acetate(10 mL), filtered through a pad of Celite, and followed by extractionwith ethyl acetate for three times. The combined organic layer wasdried over anhydrous Na2SO4, filtered, and evaporated under reducedpressure. The residual was purified by flash chromatographyon silica gel (ethyl acetate/hexane) to give the desired product.4.3.16 2-[3-(Pyridin-3-yl)phenyl]benzoxazole (3pa) Yellow solid, mp 102-103 C; 1H NMR (400 MHz, CDCl3): δ=8.96 (s, 1H), 8.66 (d, J=3.80 Hz, 1H), 8.50 (s, 1H), 8.30 (d, J=7.76 Hz, 1H), 7.89 (d, J=7.84 Hz, 1H), 7.80-7.81 (m, 1H), 7.76 (d, J=7.80 Hz, 1H), 7.67-7.60 (m, 2H), 7.43-7.37 (m, 3H); 13C NMR (100 MHz, CDCl3): δ=110.7, 120.1, 123.7, 124.8, 125.4, 126.3, 127.1, 128.1, 129.8, 130.1, 134.5, 135.7, 138.7, 142.0, 148.3, 149.1, 150.8, 162.6; HRMS-ESI (m/z): [M+H]+ calcd for C18H13N2O+: 273.1022, found: 273.1027. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With dipotassium peroxodisulfate; silver(I) nitrite; oxygen; palladium diacetate; at 130℃; for 42h;Sealed tube; | General procedure: Compound 1 or 3 (0.5 mmol), Pd(OAc)2 (11.2 mg, 0.05mmol), AgNO2 (230.8 mg, 1.5 mmol), K2S2O8 (270.3 mg, 1.0 mmol) and anhydrous TCP (2 mL) were sequentially added to a 25 mL Schlenk-flask equipped with a high-vacuum PTFE valve-to-glass seal. Then the flask was sealed and stirred at 130 C under O2 for 42 h. Upon completion, the resulting mixture was diluted with CH2Cl2 (10 mL) and then treated with 10mL of saturated Na2S aqueous solution. After filtered through a pad of Celite, the organic and aqueous layers were separated, and the aqueous layer was extracted with CH2Cl2 (2×10 mL). The combined organic layers were dried over Na2SO4 and filtered. After evaporation of the solvent under vacuum, the residue was purified by column chromatography on silica gel (100-200 mesh) using hexane-EtOAc as eluent (10:1, v/v) to give desired product 2 or 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63.6% | With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene;Reflux; | 1.75 g (6.36 mmol) of Int.2, Intermediate 5 (3.00 g, 6.36 mmol), 0.37 g (0.32 mmol) of Pd (PPh3) 4, 40 mL of toluene, 10 mL of EtOH, 10 mL of H2O and 4.05 g (19.1 mmol) of K3PO4 were mixed, It was refluxed. After the reaction was completed, the reaction mixture was cooled at room temperature and the resulting solid was filtered with EtOH. The solid was dissolved in chloroform and purified by silica gel column chromatography (CHCl3). Solidification with dichloromethane (DCM) and filtration gave 2.2 g (yield: 63.6%) of compound 4-41 (WS16-30-173) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75.6% | With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene;Reflux; | 1.45 g (5.30 mmol) of Int.2, 2.50 g (5.30 mmol) of intermediate (8), 0.31 g (0.27 mmol) of Pd(PPh3)4, 40 mL of toluene, 10 mL of EtOH, 10 mL of H2O and 3.38 g (15.9 mmol) of K3PO4 were mixed, It was refluxed. After the reaction was completed, the reaction mixture was cooled at room temperature and the resulting solid was filtered with EtOH. The solid was dissolved in chloroform and purified by silica gel column chromatography (CHCl3). Solidification with dichloromethane (DCM) and filtration gave 2.2 g (yield: 75.6%) of compound 4-227 (WS16-35-009) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38.8% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene;Reflux; | In a two-neck 250 mL flask, 2.5 g (5.12 mmol) of Int.2, 1.54 g (5.63 mmol) of intermediate 13, 0.29 g (0.25 mmol) of Pd(PPh3)4, 100 mL of toluene, 50 mL of EtOH and 5.12 mL (10.2 mmol) of 2M K2CO3 were mixed, it was refluxed. After the reaction was completed, the reaction mixture was cooled at room temperature and the resulting solid was filtered with EtOH. The solid was dissolved in chloroform and purified by silica gel column chromatography (CHCl3: HEX). Ethyl acetate (EA) was collected by filtration to obtain a beige solid 1.10 g (Yield: 38.8%) of Compound 4-413 (WS16-30-212) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.4% | With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In dichloromethane; at 20℃; for 24h; | The intermediate (31) was dissolved in 370 mL of dichloromethane and then stirred at room temperature with 2,3-dichloro-5,6-dicyano-p-benzoquinone 22.8 g (0.10 mol) of (2,3-Dichloro-5,6-dicyano-p-benzoquinone, DDQ) was slowly added. After stirring for one day it was purified using column chromatography (DCM). Solidification with methanol yielded 30.5 g (yield: 94.4%) of a white solid compound (intermediate (32)). |
45.2% | With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In dichloromethane; at 20℃; for 1h; | 66.4 g of the intermediate 20 (0.24 mol) and 1.19 L of dichloromethane were put into a 1-neck round flask, and 59.6 g of DDQ (0.26 mol) was slowly and divisionally added thereto at room temperature and reacted for 1 hour with stirring. After completion of the reaction, the reaction product was filtered through a silica plug and then, the filtrate was concentrated under reduced pressure. The concentrate was purified with ethyl acetate/methanol solvent to obtain 29.7 g of white solid compound (intermediate 21) (yield: 45.2%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With caesium carbonate; In water; for 0.166667h;Microwave irradiation; | General procedure: Add 2 ml of water to the microwave reactor,1 mmol of benzamide and 0.2 mmol of cesium carbonate were reacted in a microwave power of 120 W for 10 min.Extracted with ethyl acetate and concentrated under reduced pressure.A white solid was obtained in a yield of 99%. |
88% | With acetic acid; at 20℃; for 0.333333h; | General procedure: Add 1 ml of catalytic amount of glacial acetic acid to the mortar.1 mmol of o-aminophenol,1.2 mmol of benzaldehyde was rapidly ground at room temperature for 20 minutes.The product was extracted with ethyl acetate and water.Reduced pressure,The product was purified by column chromatography to give a pale yellow solid.The yield was 88%. |
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