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Chemical Structure| 52780-15-1 Chemical Structure| 52780-15-1

Structure of 52780-15-1

Chemical Structure| 52780-15-1

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Product Details of [ 52780-15-1 ]

CAS No. :52780-15-1
Formula : C8H6BrN
M.W : 196.04
SMILES Code : BrC1=CC=CC(=C1C)C#N
MDL No. :MFCD09025665
InChI Key :VJMRAGHVKBZNAF-UHFFFAOYSA-N
Pubchem ID :23433537

Safety of [ 52780-15-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P301+P312

Computational Chemistry of [ 52780-15-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 43.82
TPSA ?

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

23.79 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.1
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

2.7
Log Po/w (WLOGP)?

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

2.63
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.

2.52
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

2.94
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.58

Water Solubility

Log S (ESOL):?

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

-3.2
Solubility 0.124 mg/ml ; 0.00063 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.

-2.85
Solubility 0.275 mg/ml ; 0.0014 mol/l
Class?

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

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

-3.73
Solubility 0.0368 mg/ml ; 0.000188 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.

-5.58 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

2.0
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)

1.88

Application In Synthesis of [ 52780-15-1 ]

* 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 [ 52780-15-1 ]

[ 52780-15-1 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 52780-15-1 ]
  • [ 199609-62-6 ]
  • [ 943722-03-0 ]
YieldReaction ConditionsOperation in experiment
92% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 120℃; for 2h; Example 16. Synthesis of N-[3'-(aminomethyl)-2-methylbiphenyl-3-yl]methyl}-5- nitro-4-(4,5,7,8-tetrahydroimidazo[4,5-d]azepin-6(lH)-yl)pyrimidin-2-amine; A solution of 3-bromo-2-methyl-benzamide (500 mg, 2.340 mmol) and pyridine (0.60 mL, 7.42 mmol) in dichloromethane (10 mL) was cooled to 0 0C and treated with trifluoroacctic anhydride (1.0 mL, 7.08 mmol). The reaction mixture was warmed to room temperature and stirred for 15 h, then partitioned between ethyl acetate (100 mL) and 1 M HCl solution (25 mL). The organic phase was washed with satd NaHCOs solution (25 mL) and brine (25 mL), dried over Na2SO4, filtered and concentrated to afford 423 mg (92%) of 3-bromo-2-methyl-benzonitrile as a pale yellow oil that was carried on without further purification.To a mixture of 3-bromo-2-mcthyl-bcnzonitrilc (400 mg, 2.04 mmol), [3-N-boc- aminomethyl)phenyl]boronic acid (768 mg, 3.06 mmol), tetrakis(triphenylphosphine)palladium (236 mg, 0.204 mmol), and sodium carbonate (649 mg, 6.12 mmol) was added dimethoxyethane (16 mL) and water (1.6 mL). The reaction mixture was sealed under N2 and heated at 120 C for 2 h. The reaction mixture was partitioned between ethyl acetate (125 mL) and 5% NaCl solution (40 mL). The organic <n="48"/>phase was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography eluting with 5-15% ethyl acetate in hexanes to furnish 604 mg (92%) of (3'-cyano-2'-methyl-biphenyl-3-ylmethyl)-carbamic acid tert- butyl ester, m/z 323.5 (M + H)+.A solution of (3'-cyano~2'-methyl-biphenyl-3-ylmethyl)-carbamic acid te/Y-butyl ester (100 mg, 0.31 mmol) and cobaltous chloride hexahydrate (111 mg, 0.47 mmol) in 2:1 THF/H2O (3 mL) was cooled to 0 C and treated with sodium borohydride (59 mg, 1.55 mmol), portionwise over several minutes. The reaction mixture was warmed to room temperature and stirred for 1 h. After the addition of 1 mL of cone NH4OH, the mixture was stirred for 5 min and then filtered, washing the collected solids with 2:1 THF/H2O (20 mL). The filtrates were concentrated, and the residue was partitioned between dichloromethane (15 mL) and water (5 mL). The aqueous phase was extracted with dichloromethane (2x15 mL), and the combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated to furnish 74 mg (73%) of (3'-aminomcthyl-2'-mcthyl-biphcnyl-3- yhnethyl)-carbamic acid tert-bvyl ester as an off-white solid, m/z 327.6 (M + H)+. (Osby, J. O.; Heinzman, S. W.; Ganem, B. J. Am. Chem. Soc. 1986, 108, 67-72).To a solution of (3'-aminomethyl-2'-methyl-biphenyl-3-ylmethyl)-carbamic acid tert-butyl ester (76 mg, 0.23 mmol) and diisopropylethylamine (0.045 mL, 0.26 mmol) in dichloromethane (2.0 mL) was added 2-chloro-5-nitro-4-thiocyanato-pyrimidine (50 mg, 0.23 mmol). The rxn mixture was stirred at room temperature for 72 h, then diluted with 5% MeOH in CH2Cl2 (30 mL) and washed with 1 M HCl solution (8 mL). The organic phase was washed with satd NaHCO3 solution and brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography eluting with 15-30% ethyl acetate in hexanes to afford 74 mg (63%) of {2'-methyl-3'-[(5-nitro-4- thiocyanato-pyrimidin-2-ylamino)-methyl]-biphenyl-3-ylmethyl}-carbamic acid tert-buty ester, m/z 507.5 (M + H)+.To a solution of 1 ,4,5,6,7,8-hexahydro-iτnidazo[4,5-<i]azepine, di-HCl salt (37 mg, 0.18 mmol) and diisopropylethylamine (0.102 mL, 0.58 mmol) in 3:1 dichloromethane/JV,N- dimethylformamide (2.0 mL) was added {2'-methyl-3'-[(5-nitro-4-thiocyanato-pyrimidin- 2-ylamino)-methyl]-biphenyl-3-ylmethyl} -carbamic acid tert-butyl ester (74 mg, 0.15 <n="49"/>mmol). The rxn mixture was stirred at room temperature for 7.5 h, then diluted with ethyl acetate (35 mL) and washed with 5% NaCl solution (3*12 mL) and brine (15 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography eluting with 0-5% MeOH in CH2Cl2 to give 63 mg (74%) of (2'-methyl- 3'-[5-nitro-4-(4,5,7,8-tetrahydro-lH-imidazo[4,5-r|azepm-6-yl)-pyrimidin-2-ylamino]- methyl}-biphenyl-3-ylmethyl)-carbamic acid tert-butyl ester, m/z 585.8 (M + H)+.A solution of (2I-methyl-3'-[5-nitro-4-(4,5J7,8-tetrahydro-lH-imidazo[4,5-
  • 2
  • [ 52780-15-1 ]
  • [ 109179-31-9 ]
 

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