Structure of 626-39-1
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CAS No. : | 626-39-1 |
Formula : | C6H3Br3 |
M.W : | 314.80 |
SMILES Code : | BrC1=CC(Br)=CC(Br)=C1 |
MDL No. : | MFCD00000080 |
InChI Key : | YWDUZLFWHVQCHY-UHFFFAOYSA-N |
Pubchem ID : | 12279 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 49.54 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.69 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.51 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.97 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.51 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.9 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.92 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.13 |
Solubility | 0.00235 mg/ml ; 0.00000747 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.23 |
Solubility | 0.0185 mg/ml ; 0.0000587 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.93 |
Solubility | 0.00366 mg/ml ; 0.0000116 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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 |
-5.02 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
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) |
1.5 |
* 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 |
---|---|---|
In N,N-dimethyl-formamide; at 90℃; for 0.25h; | Sodium methoxide (25 g; WAKO) was added to a DMF (250 mL) solution of 1,3,5-tribromobenzene (75 g; TCI) and the resulting mixture was stirred at 90° C. for 15 minutes. The reaction mixture was concentrated, aqueous ammonium chloride (400 mL) and ethyl acetate (400 mL) were added to extract the reaction mixture, the organic layer was washed with saturated brine (200 mL.x.2), and the organic layer was dried. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography (n-hexane) to give the title compound (39.2 g).1H-NMR (CDCl3); 8 (ppm) 3.97 (3H, s), 6.98 (2H, m), 7.25 (1H, m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; n-butyllithium; benzaldehyde; | Step 1: (3,5-dibromo-phenyl)-phenyl-methanol E3-A To a solution of 1,3,5-tribromobenzene (10 g, 0.0318 mole) in ether (500 g), under argon was added nBuLi in hexanes (13.4 mL, 0.0318 mole) dropwise at -78 C. During the intial cooling of the tribrombenzene in ether some solids crashed out of solution. After addition of nBuLi was complete the reaction was allowed to stir for 0.5 hours at which time neat benzaldehyde (3.55 mL, 0.035 mole) was added dropwise to the vigorously stirred reaction mixture. Once addition was complete the reaction was allowed to reach 0 C. and 100 mL of HCl was added to the mixture. This was extracted with ether two times, dried with brine and over sodium sulfate and concentrated to give an oil. The crude product was purified by chromatography with 5% EtOAc/Hexanes to afford E3-A as a colorless oil that solidified on the bench. Rf=0.44 (5%EtOAc/Hexanes) 1H NMR (400MHz, CDCl3) δ7.56-7.55 (m, 1H), 7.48-7.47 (m, 2H), 7.39-7.29 (m, 5H), 5.75 (d, 1H, j=3.48 Hz), 2.28-2.27 (d, 1H, j=3.48 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 2,3,5-trimethyl-pyridine; hexane; mineral oil; | PREPARATION 6 3-(3,5-Dibromophenoxy)pyridine Sodium hydride (3.24 g of a 60% dispersion in mineral oil) was added portionwise to a stirred mixture of 3-hydroxypyridine (15.4 g), 1,3,5-tribromobenzene (76.4 g), cuprous oxide (11.6 g) and collidine (400 ml). When evolution of hydrogen had ceased, the mixture was heated at 200 for 8 hours and then cooled. The cool mixture was diluted with ethyl acetate and water, basified with aqueous ammonia (SG 0.880) and then filtered. The filtered residue was washed with ethyl acetate, then the washings and organic phase of the filtrate combined, washed with saturated brine and dried (MgSO4). The ethyl acetate was evaporated under vacuum, the collidine removed by distillation under vacuum and the residue chromatographed on silica gel using ether:hexane (1:4) as eluent. The earlier fractions gave, after evaporation under vacuum, recovered tribromobenzene (42.5 g). The later fractions were evaporated under vacuum to afford the title compound as an oil (18.55 g); δ (CDCl3): 7.07(2H,s), 7.22-7.26(2H,m), 7.42 (1H,s), 8.42(1H,s), 8.47(1H,d). Found: C,40.49; H,2.17; N,4.19. C11 H7 Br2 NO requires C,40.16; H,2.14; N,4.26%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.3 g | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; for 24h;Inert atmosphere; Reflux; | Intermediate 2 (2 g, 3.7 mmol), 1,3,5-tribromo benzene (5.9 g, 18.7 mmol), tetrakis (triphenylphosphine) palladium (0) (0.1 g, 0.1 mmol) in the THF It was dissolved in a nitrogen stream. Put potassium carbonate (1 M, 30 ml) was stirred and refluxed for 24 hours up to temperature. After the distilled water and extracted with MC, by the MC / Hexane solvent mixture as a developing solvent to conduct column chromatography to give the intermediate 3 in 1.3 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | Tert-butyllithium in pentane (1.6M, 7.72 mL) was added dropwise to a solution of 1 ,3,5 tribromobenzene (0.972 g, 3.09 mmol) in anhydrous ether (30 mL) at -78 C under a flow of nitrogen gas. After 2 h, 2-Fluoro-/V-methoxy-/V- methyl-benzamide (1.132 g, 6.18 mmol) dissolved in anhydrous ether (5 mL) was added dropwise and the reaction mixture was allowed to slowly come to room temperature and stirred for 24 h. After 24 h, the reaction mixture was quenched with water (30 ml_) and the products were extracted with ether (2 x 50 ml_). The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Purification using flash chromatography (silica gel, hexanes:ethyl acetate, gradient 95:5 to 60:40) afforded 2-1 ,3-bis(2-fluoro-benzoyl)-5-bromobenzene 10 (0.617 g, 6.18 mmol) in a 50% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; for 72h;Inert atmosphere; Reflux; | A mixture of aniline (7.4 g, 79.4 mmol), 1,3,5-tribromobenzene 3 (5.0 g, 15.88 mmol), tris(dibenzylideneacetone) dipalladium(0) [Pd2(dba)3(0), 0.11 g, 0.25 mol %], rac-2,2'-bis(diphenylphosphino)-1,1'-binapthyl (BINAP, 0.22 g, 0.75 mol %), and sodium t-butoxide (7.63 g, 79.4 mmol) in anhydrous toluene (250 mL) was heated to refluxing temperature under nitrogen for a period of 72 h. The reaction mixture was cooled to room temperature and washed with water (100 mL). The organic layer was dried over anhydrous sodium sulfate (Na2SO4). After evaporation of the solvent, a crude brown color solid was obtained. Excess aniline was then removed by distillation at 130 C under reduced pressure of 101 mmHg. It was further purified by chromatography (SiO2). The resulting light brown product 1,3,5-tris(phenylamino)benzene 4, TPAB, was obtained in 75% yield (4.18 g). FT-IR (KBr) upsilonmax 3403 (m), 3375 (m), 3078 (w), 3019 (w), 2945 (s), 1612 (m), 1591 (vs), 1518 (m), 1496 (s), 1469 (m), 1431(w), 1456 (m), 1409 (m), 1365 (w), 1295 (m), 1269 (w), 1246 (m), 1,171 (m), 1073 (w), 1030 (w), 897 (w), 834 (w), 820 (w), 802 (w), 756 (m), 721 (w), 700 (m), 688 (m), 613 (w), and 558 (w) cm-1; UV-vis (CHCl3, 1.0 × 10-5 M) lambdamax (epsilon) 289 nm (4.80 × 104 L mol-1 cm-1); 1H-NMR (500 MHz, CDCl3) delta 7.25 (t, J = 7.8 Hz, 6H), 7.08 (d, J = 7.7 Hz, 6H), 6.92 (t, J = 7.3 Hz, 3H), 6.32 (s, 3H), and 5.60 (s, 3H, N-H); 13C-NMR (125 MHz, CDCl3) delta 145.4, 142.7, 129.3, 121.3, 118.7, and 99.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | tert-Butyllithium in pentane (1.6 M, 7.72 mL) was added dropwise to a solution of 1,3,5-tribromobenzene (0.972 g, 3.09 mmol) in anhydrous ether (30 mL) at -78 C under a flow of nitrogen gas. After 2 h, <strong>[198967-24-7]2-fluoro-N-methoxy-N-methyl-benzamide</strong> (1.132 g, 6.18 mmol) dissolved in anhydrous ether (5 mL) was added dropwise and the reaction mixture was allowed to slowly come to room temperature and stirred for 24 h. After 24 h, the reaction mixture was quenched with water (30 mL) and the products were extracted with ether (2 * 50 mL). The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Purification using flash chromatography (silica gel, hexanes/ethyl acetate, gradient 95:5 to 60:40) afforded 1,3-bis(3-fluorobenzoyl)-5-bromobenzene (0.617 g, 6.18 mmol, 50% yield). 1H NMR (500 MHz, CDCl3): delta 8.16 (2H, m), 8.12 (1H, pentet, J = 1.4 Hz), 7.61-7.56 (4H, m), 7.30 (2H, td, J = 7.5 Hz, 1.0 Hz), 7.20-7.16 (2H, m). 13C NMR (125 MHz, CDCl3): delta 191.23, 160.40 (d, J = 254 Hz), 139.67, 133.61, 134.29 (d, J = 8.6 Hz), 131.12 (d, J = 1.9 Hz), 129.31, 125.79 (d, J = 13.8 Hz), 124.79 (d, J = 3.8 Hz), 123.18, 116.70 (d, J = 21 Hz). 19F NMR (470 MHz, CDCl3): delta -109.73 to -109.78 (1F, m). HRMS (ESI) calculated for C20H11BrF2O2H+ (M+H)+ 400.99833, found 400.99857. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 24h;Reflux; | Sub 1-1 (5.0g, 16mmol) and Sub 1-1-2 (6.7g, 18mmol), Pd (PPh3)4 (0.06g, 0.05mmol) and K2CO3 (6.6 g, 48mmol) were dissolved in anhydrous THF and a small amount of water, and refluxedfor 24 hours. When the reaction is complete, thereaction mixture is cooled to room temperature, extracted with CH2Cl2 and washed with water. A small amount of water is removed by drying over anhydrous MgSO4, and concentrated under reduced pressure after filtration, and subjected to column chromatography to obtain 5.6g of the product Sub 1-2 (2). (Yield: 74%) |
66% | With tetrakis(triphenylphosphine) palladium(0); sodium hydroxide; In tetrahydrofuran; water; at 80℃; | The M2-1 (51.84 g, 139.6 mmol) in a round bottom flask, THF (700 ml) to dissolve later, 1,3,5-tribromobenzene (87.91 g, 279.3 mmol), Pd(PPh3)4 (4.84 g, 4.2 mmol), NaOH (16.76 g, 418.9 mmol), water (350 ml) was added and the mixture was stirred at 80 . When the reaction is complete, water and CH2Cl2 and the organic layer was dried over MgSO4, and extracted with silicagel column and re-crystallization and the resulting compound then concentrated product was 44.16 g (yield: 66%) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16.8 mg | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 100℃; for 22h;Inert atmosphere; | 1-bromo-3,5-di-tert-butylbenzene (20.1 g, 77.4 mmol) was dissolved in THF (400 mL) underAr at ?78 °C. 1.64 M solution of n?BuLi in n-Hexane (100 mL, 164 mmol) was slowly added.After the solution was stirred at ?78 °C for 1.5 h, triisopropyl borate (44.0 mL, 189 mmol)dissolved in THF (60.0 mL) was immediately added. The solution was stirred overnight atroom temperature. Et2O and 10percent HCl aq. were added to the solution, the organic layer wasseparated and dried over MgSO4, then filtered. The solvent was removed by evaporation toyield 2 as a white solid (21.2 g, crude). And 2, 1,3,5-tribromobenzene (48.7 g, 155 mmol),Pd(PPh3)4 (1.79 g, 1.55 mmol), Na2CO3 (16.4 g, 155 mmol) were dissolved in toluene (678 mL),EtOH (255 mL) and H2O (110 mL) under Ar. The solution was stirred 22 h at 100 °C. Et2O andCH2Cl2 was added to the solution and the organic layer was separated and dried over MgSO4,and then filtered. The solvent was removed by evaporation, and the residue was purified by column chromatography on silica gel (eluent : n-Hexane) to yield 3 as a white solid (16.8 g,39.6 mmol, 2 steps 63 percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75 mmol | Step1. Will be tribromobenzene 100mmol,After adding anhydrous THF to dissolve, cooling to -78 C,Add 220 mmol of n-butyl lithium,The reaction was carried out under nitrogen for 1 hour.Add 210 mmol of triphenylchlorodecane,Replace argon three times again, gradually warmed to room temperature and continued to react for 6 h.After the reaction is completed,Pour deionized water, the crude product is precipitated,filter,Rinse with water,After drying, column chromatography,The product was obtained in 7-1, 75 mm |
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