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Chemical Structure| 626-39-1 Chemical Structure| 626-39-1

Structure of 626-39-1

Chemical Structure| 626-39-1

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Product Details of [ 626-39-1 ]

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

Safety of [ 626-39-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 626-39-1 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

2.69
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

4.51
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

3.97
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

4.51
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

3.9
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.92

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-5.13
Solubility 0.00235 mg/ml ; 0.00000747 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-4.23
Solubility 0.0185 mg/ml ; 0.0000587 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-4.93
Solubility 0.00366 mg/ml ; 0.0000116 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

Yes
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.02 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

1.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.5

Application In Synthesis of [ 626-39-1 ]

* 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.

  • Downstream synthetic route of [ 626-39-1 ]

[ 626-39-1 ] Synthesis Path-Downstream   1~23

  • 1
  • [ 626-39-1 ]
  • [ 124-41-4 ]
  • [ 626-41-5 ]
  • [ 74137-36-3 ]
  • 2
  • [ 626-39-1 ]
  • [ 626-41-5 ]
  • [ 74137-36-3 ]
  • 3
  • [ 626-39-1 ]
  • [ 124-41-4 ]
  • [ 74137-36-3 ]
YieldReaction ConditionsOperation 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)
  • 5
  • [ 615-54-3 ]
  • [ 7664-41-7 ]
  • sodium amide [ No CAS ]
  • [ 626-39-1 ]
  • [ 615-55-4 ]
  • 6
  • [ 626-39-1 ]
  • [ 626-00-6 ]
  • [ 626-44-8 ]
  • [ 149428-64-8 ]
  • 7
  • [ 626-39-1 ]
  • [ 124-41-4 ]
  • [ 621-23-8 ]
  • [ 20469-65-2 ]
  • [ 74137-36-3 ]
  • 9
  • [ 626-39-1 ]
  • [ 608-21-9 ]
  • [ 51339-31-2 ]
YieldReaction ConditionsOperation 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).
  • 10
  • [ 109-00-2 ]
  • [ 626-39-1 ]
  • [ 146060-06-2 ]
  • [ 608-21-9 ]
  • [ 145691-56-1 ]
YieldReaction ConditionsOperation 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%.
  • 11
  • [ 626-39-1 ]
  • [ 74137-36-3 ]
  • 13
  • [ 626-39-1 ]
  • [ 197223-39-5 ]
  • [ 120046-02-8 ]
  • 14
  • [ 626-39-1 ]
  • [ 1082549-89-0 ]
  • [ 1233491-85-4 ]
YieldReaction ConditionsOperation 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.
  • 16
  • [ 626-39-1 ]
  • [ 128733-85-7 ]
  • [ 1422465-68-6 ]
  • 17
  • [ 626-39-1 ]
  • [ 128733-85-7 ]
  • [ 1422465-69-7 ]
  • 18
  • [ 198967-24-7 ]
  • [ 626-39-1 ]
  • [ 1458033-50-5 ]
YieldReaction ConditionsOperation 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.
  • 19
  • [ 626-39-1 ]
  • [ 62-53-3 ]
  • [ 102664-66-4 ]
YieldReaction ConditionsOperation 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.
  • 20
  • [ 198967-24-7 ]
  • [ 626-39-1 ]
  • 1,3-bis(3-fluorobenzoyl)-5-bromobenzene [ No CAS ]
YieldReaction ConditionsOperation 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.
  • 21
  • [ 267221-88-5 ]
  • [ 626-39-1 ]
  • [ 1258948-07-0 ]
YieldReaction ConditionsOperation 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.
  • 22
  • [ 626-39-1 ]
  • [ 197223-39-5 ]
  • 3,5-dibromo-3',5'-di-tert-butylbiphenyl [ No CAS ]
YieldReaction ConditionsOperation 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).
  • 23
  • [ 626-39-1 ]
  • [ 1626-24-0 ]
  • C42H33BrGe2 [ No CAS ]
YieldReaction ConditionsOperation 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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Technical Information

Categories

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