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Structure of 540516-28-7

Chemical Structure| 540516-28-7

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Product Details of [ 540516-28-7 ]

CAS No. :540516-28-7
Formula : C8H7BrN2O
M.W : 227.06
SMILES Code : OCC1=NC2=CC(Br)=CC=C2N1
MDL No. :MFCD03197450
InChI Key :RXQCVQKHRKONLO-UHFFFAOYSA-N
Pubchem ID :4162824

Safety of [ 540516-28-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 540516-28-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 9
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 49.92
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

48.91 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.73
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

1.33
Log Po/w (WLOGP)?

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

1.67
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.

1.18
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

2.51
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.48

Water Solubility

Log S (ESOL):?

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

-2.57
Solubility 0.605 mg/ml ; 0.00266 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-1.96
Solubility 2.5 mg/ml ; 0.011 mol/l
Class?

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

Very 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

-3.6
Solubility 0.057 mg/ml ; 0.000251 mol/l
Class?

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

Soluble

Pharmacokinetics

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)
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

No
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.

-6.74 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

0.0
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

0.0
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)

1.79

Application In Synthesis of [ 540516-28-7 ]

* 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 [ 540516-28-7 ]

[ 540516-28-7 ] Synthesis Path-Downstream   1~10

  • 2
  • [ 540516-28-7 ]
  • [ 1005333-30-1 ]
  • [ 1005333-29-8 ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; hydroxylamine-O-sulfonic acid; In water; at 40 - 50℃; for 0.5h; Example 15. Production of intermediate compounds (l-amino-5-bromo-lH- benzimidazol-2-yl)methanol (compound 17) and (l-amino-6-bromo-lH-benzimidazol-2- yl)methanol (compound 18).The 5(6)-bromo-lH-benzimidazol-2-methanol (16 a, b) (5.2 g, 22.7 mmol), prepared to known methodology, is dissolved in a solution of KOeta (4.8 g, 72.8 mmol) in H2O (40 niL). To the mixture is added under stirring at 400C solution Of NH2OSO3H (6g, 50mmol) in H2O (15 mL), neutralized NaHCO3. Upon the completion of the exothermal reaction the mixture is still incubated at 40-500C for 0.5 h and then cooled to room temperature. The resultant precipitate is filtered and recrystallization is accomplished from water. The mixture of compounds 17 and 18 is obtained in 1 :1 ratio (according to 1H NMR). The mixture of these compounds is crystalline, white.Overall yield: 3.7g (67%). 1H NMR (300 MHz, DMSO-d6): delta ppm 4.73 (4H, s, 2CH2), 5.43 (IH, s, OH), 5.45 (IH, s,OH), 6.01 (2H, s, NH2), 6.03 (2H, s, NH2), 7.31 (IH, d, J- 9Hz, ArH), 7.39 (IH, d, J= 9Hz, ArH), 7.46 (IH, d, J- 9Hz, ArH), 7.53 (IH, d, J= 9Hz, ArH), 7.67 (IH, s, ArH), 7.73 (IH, s, ArH).13C NMR (75 MHz, DMSO-d6): delta ppm 55.81, 55.81, 112.48, 113.46, 114.15, 114.98, 121.46, 122.01, 124.93, 125.36, 135.73, 137.78, 139.62, 141.88, 156.17, 156.48. IR (v, cm"1): 3350, 3313, 3184, 3120 NH2.Analysis (C8H8BrN3O): calcd: C 39.67%, H 3.31 %, N 17.36%; found: C 39.88%, H 3.52%, N 17.46%.
  • 3
  • [ 540516-28-7 ]
  • [ 1005333-31-2 ]
  • [ 1005333-32-3 ]
YieldReaction ConditionsOperation in experiment
25%; 25% Example 15. Production of intermediate compounds (l-amino-5-bromo-lH- benzimidazol-2-yl)methanol (compound 17) and (l-amino-6-bromo-lH-benzimidazol-2- yl)methanol (compound 18).The 5(6)-bromo-lH-benzimidazol-2-methanol (16 a, b) (5.2 g, 22.7 mmol), prepared to known methodology, is dissolved in a solution of KOeta (4.8 g, 72.8 mmol) in H2O (40 niL). To the mixture is added under stirring at 400C solution Of NH2OSO3H (6g, 50mmol) in H2O (15 mL), neutralized NaHCO3. Upon the completion of the exothermal reaction the mixture is still incubated at 40-500C for 0.5 h and then cooled to room temperature. The resultant precipitate is filtered and recrystallization is accomplished from water. The mixture of compounds 17 and 18 is obtained in 1 :1 ratio (according to 1H NMR). The mixture of these compounds is crystalline, white.Overall yield: 3.7g (67%). 1H NMR (300 MHz, DMSO-d6): delta ppm 4.73 (4H, s, 2CH2), 5.43 (IH, s, OH), 5.45 (IH, s,OH), 6.01 (2H, s, NH2), 6.03 (2H, s, NH2), 7.31 (IH, d, J- 9Hz, ArH), 7.39 (IH, d, J= 9Hz, ArH), 7.46 (IH, d, J- 9Hz, ArH), 7.53 (IH, d, J= 9Hz, ArH), 7.67 (IH, s, ArH), 7.73 (IH, s, ArH).13C NMR (75 MHz, DMSO-d6): delta ppm 55.81, 55.81, 112.48, 113.46, 114.15, 114.98, 121.46, 122.01, 124.93, 125.36, 135.73, 137.78, 139.62, 141.88, 156.17, 156.48. IR (v, cm"1): 3350, 3313, 3184, 3120 NH2.Analysis (C8H8BrN3O): calcd: C 39.67%, H 3.31 %, N 17.36%; found: C 39.88%, H 3.52%, N 17.46%. Example 16. Production of intermediate compounds 3-chloro-6- bromobenzimidazo[l,2-c][l,2,3]thiadiazole (compound 19) and 3-chloro-7- bromobenzimidazo[l,2-c][l,2,3]thiadiazole (compound 20).The mixture of (l-amino-5-brorno-lH-benzimidazol-2-yl)-methanol (compound 17) and (l-amino-6-bromo-lH-benzimidazol-2-yl)-methanol (compound 18) (0.5 g, 2.1 mmol) is refluxed with SOCl2 (5 mL) for 0.5 h. The excess of SOCl2 is evaporated. The residue is washed (NaHCO3ZH2O, H2O). The mixture of products consists of compounds 19 and 20 in proportion 1: 1. The compounds were separated by flash chromatography (dichlormethane: ethy lacetate= 10:1). Overall yield: 0.36 g (60%) (recrystallization is accomplished from methanol).20: Yield: 0.15g (25%), mp 193-1940C. Rf= 0.48 (dichlormethane: ethylacetate=10:l).1H NMR (300 MHz, DMSO-d6): 7.7 (IH, dd, J= 2 and 9Hz, CH(6)), 7.79 (IH, dd, J= 0.5Hz and 9Hz, CH(5)), 8.46 (IH, dd, J= 0.5 and 2Hz, CH(8)). 13C NMR (75 MHz, DMSO-d6): 112.76, 116.24, 123.03, 126.61, 129.36, 131.66, 151.72,152.49.Analysis (C8H3BrClN3S): calcd: C 33.30%, H 1.05 %, N 14.56%; found: C 33.56%, H 1.15%, N 14.63%.3-chloro-6-bromobenzimidazo[l,2-c][l,2,3]thiadiazole (compound 19) yield: 0,15g (25%), mp l53-154C.Rf= 0.59 (dichlormethane: ethylacetate=10:l).1H NMR (300 MHz, DMSO-d6): 7.45 (IH, dd, J= 2 and 9Hz, CH(7)), 8.07 (IH, d, J= 2Hz, CH(5)), 8.19 (IH, d, J= 9Hz, CH(8)).13C NMR (75 MHz, DMSO-d6): 115.36, 121.57, 123.38, 123.77, 127.76, 129.38, 152.77, 154.55.Analysis (C8H3BrClN3S): calc: C 33.30 %, H 1.05 %, N 14.56 %; found: C 33.01 %, H 1.33 %, N 14.36 %).
  • 4
  • [ 7051-34-5 ]
  • [ 540516-28-7 ]
  • [ 1100215-83-5 ]
  • [ 1100215-82-4 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; In N,N-dimethyl-formamide; at 50℃; for 19h; A 0.1 M solution of 5-Bromo-1H-benzo[d]imidazol-2-yl)methanol (630 mg, 2.8 mmol) in dimethylformamide was stirred with 2.4 equiv of cesium carbonate and (0.3 mL, 1.2 equiv) of cyclopropylmethyl bromide at 50 C. for 19 h. At the end dimethylformamide was evaporated in vacuo. The residue was partitioned between ethyl acetate (70 mL) and water (30 mL). Organic layer was dried (sodium sulfate) and evaporated in vacuo to give 800 mg of crude product which by LC-MS was 75% pure. LC/MS (HPLC method 1): tR=2.1 min, 281(MH)+. Silica gel TLC (ethyl acetate:hexane=4: 1) revealed two major products with Rf=0.29 and 0.20, which without separation were used in the next step.
  • 5
  • [ 832114-00-8 ]
  • [ 540516-28-7 ]
  • [ 1613695-43-4 ]
  • 6
  • [ 24424-99-5 ]
  • [ 540516-28-7 ]
  • tert-butyl 5-bromo-2-(((tert-butoxycarbonyl)oxy)methyl)-1H-benzo[d]imidazole-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; triethylamine; In dichloromethane; at 25℃; for 4h; Into a 50-mL round-bottom flask, was placed (5-bromo-lH- l,3-benzodiazol-2- yl)methanol (600 mg, 2.64 mmol, 1.00 equiv), dichloromethane (20 mL), Boc20 (1 g, 4.58 mmol, 1.73 equiv), TEA (800 mg, 7.91 mmol, 2.99 equiv), 4- dimethylaminopyridine (32 mg, 0.26 mmol, 0.10 equiv). The resulting solution was stirred for 4 h at 25C. The mixture was diluted with 20 mL of dichloromethane, washed with 3*30 mL of water and 30 mL of brine. The organic phase was dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 600 mg (crude) of the title compound as yellow oil. LC-MS (ES, m/z) 429,427[M+H]+
  • 7
  • [ 540516-28-7 ]
  • [ 1740-88-1 ]
  • 8
  • [ 540516-28-7 ]
  • [ 40197-20-4 ]
YieldReaction ConditionsOperation in experiment
37% With potassium permanganate; In water; acetone; Synthesis of 5-bromo-1H-benzimidazole-2-carboxylic acid hydrochloride 44 was prepared using 5-bromo-1H-benzimidazole-2-yl)-methanol 28 (0.23 g, 1.0 mmol) dissolved in acetone (10 mL) and potassium permanganate (0379, 2.4 mmol) dissolve in water (10 mL). The crude product was recrystallised from water. 5-Bromo-1H-benzimidazole-2-carboxylic acid in Yield 37% was recovered as a creamy white powder.
  • 9
  • [ 540516-28-7 ]
  • [ 74-88-4 ]
  • (N-methyl-5-bromo-1H-benzimidazole-2-yl)methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
9% N-Methyl-2-methanol 5-bromobenzimidazole 50 was prepared according to the procedure by Gonzlez-Chvez et al. [28]. A solution of 5-bromo-(1H-benzimidazole-2-yl)-methanol 28 (0.60 g, 2.60 mmol), and sodium hydroxide (0.10 g, 2.60 mmol) were stirred in dry acetone (10 mL) for 30 min. Then, iodomethane (0.37 g, 2.60 mmol) was added and the mixture was stirred for 24 h. The reaction mixture was concentrated to a quarter and then poured into ice-cold water. The solid was filtered and washed with 50% HCl. The solid was washed with water (100 mL) and purified by column chromatography (9:1 chloroform/ethanol) to give the desired product (50) as a bright yellow crystals Yield 16%.
  • 10
  • [ 79-14-1 ]
  • [ 1575-37-7 ]
  • [ 540516-28-7 ]
 

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Technical Information

Categories

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[ 540516-28-7 ]

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