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Chemical Structure| 885270-32-6 Chemical Structure| 885270-32-6

Structure of 885270-32-6

Chemical Structure| 885270-32-6

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Product Details of [ 885270-32-6 ]

CAS No. :885270-32-6
Formula : C8H8BrClO
M.W : 235.51
SMILES Code : COC1=CC(Cl)=CC(CBr)=C1
MDL No. :MFCD08234654
InChI Key :NOYAZORDAAINEF-UHFFFAOYSA-N
Pubchem ID :53403078

Safety of [ 885270-32-6 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H314
Precautionary Statements:P501-P260-P270-P264-P280-P303+P361+P353-P301+P330+P331-P363-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P405
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 885270-32-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 2
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 50.78
TPSA ?

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

9.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.6
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

3.08
Log Po/w (WLOGP)?

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

3.09
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.

3.17
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

3.46
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.08

Water Solubility

Log S (ESOL):?

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

-3.51
Solubility 0.0724 mg/ml ; 0.000307 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.

-2.94
Solubility 0.27 mg/ml ; 0.00115 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

-4.41
Solubility 0.00927 mg/ml ; 0.0000394 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

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

Yes
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.

-5.55 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

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

1.0 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)

1.8

Application In Synthesis of [ 885270-32-6 ]

* 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 [ 885270-32-6 ]

[ 885270-32-6 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 885270-32-6 ]
  • [ 143-33-9 ]
  • [ 178486-31-2 ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; (iii) (3-chIoro-5-methoxyphenyl)acetonitrilePhosphorous tribromide (0.28 ml) was added to a solution of the product of step (ii) (1.55 g) in ether (20 ml) at 0 0C, then stirred for 30 min. The reaction mixture was partitioned between ether and aqueous sodium hydrogen carbonate, the organics were separated then dried (MgSO4) and evaporated under reduced pressure. The residue was dissolved in DMF (20 ml) and sodium cyanide (0.5 g) was added. The mixture was stirred overnight then partitioned between ether and water; the organics were separated, washed with aqueous sodium hydrogen carbonate then dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography (eluent 1:1 ether/ isohexane) to give the subtitle compound (0.53g).1H NMR CDCl3-d6: delta 6.91-6.9 (IH, m), 6.86-6.85 (IH, m), 6.77-6.76 (IH, m), 3.79 (3H, s), 3.69 (2H, s).
In N,N-dimethyl-formamide;Product distribution / selectivity; (iii) (3-chloro-5-methoxyphenyl)acetonitrile Phosphorous tribromide (0.28 ml) was added to a solution of the product of step (ii) (1.55 g) in ether (20 ml) at 0 C., then stirred for 30 min. The reaction mixture was partitioned between ether and aqueous sodium hydrogen carbonate, the organics were separated then dried (MgSO4) and evaporated under reduced pressure. The residue was dissolved in DMF (20 ml) and sodium cyanide (0.5 g) was added. The mixture was stirred overnight then partitioned between ether and water; the organics were separated, washed with aqueous sodium hydrogen carbonate then dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography (eluent 1:1 ether/isohexane) to give the subtitle compound (0.53 g). 1H NMR CDCl3-d6: delta 6.91-6.9 (1H, m), 6.86-6.85 (1H, m), 6.77-6.76 (1H, m), 3.79 (3H, s), 3.69 (2H, s).
  • 2
  • [ 82477-68-7 ]
  • [ 885270-32-6 ]
YieldReaction ConditionsOperation in experiment
79% With phosphorus tribromide; In diethyl ether; at 0 - 20℃; for 2h; To a solution of (3-chloro-5-methoxyphenyl)methanol (2.0 g, 1 1 .6 mmol) in diethyl ether (20 ml_) at 0 C was added phosphorus tribromide (0.5 ml_). The reaction mixture was stirred at 0 C for 2 h. Reaction was poured into saturated aqueous sodium bicarbonate (150 ml_) and extracted with ethyl acetate (200 ml_ x 2). The combined organic phases were dried over sodium sulfate, filtered and concentrated to afford 1 -(bromomethyl)-3-chloro-5-methoxybenzene (2.15 g, 9.16 mmol, 79%) as a light-yellow solid. Used in the next step directly without additional purification.
With phosphorus tribromide; In diethyl ether; at 0℃; for 0.5h; (iii) (3-chIoro-5-methoxyphenyl)acetonitrilePhosphorous tribromide (0.28 ml) was added to a solution of the product of step (ii) (1.55 g) in ether (20 ml) at 0 0C, then stirred for 30 min. The reaction mixture was partitioned between ether and aqueous sodium hydrogen carbonate, the organics were separated then dried (MgSO4) and evaporated under reduced pressure. The residue was dissolved in DMF (20 ml) and sodium cyanide (0.5 g) was added. The mixture was stirred overnight then partitioned between ether and water; the organics were separated, washed with aqueous sodium hydrogen carbonate then dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography (eluent 1:1 ether/ isohexane) to give the subtitle compound (0.53g).1H NMR CDCl3-d6: delta 6.91-6.9 (IH, m), 6.86-6.85 (IH, m), 6.77-6.76 (IH, m), 3.79 (3H, s), 3.69 (2H, s).
With phosphorus tribromide; In diethyl ether; at 0℃; for 0.5h; Phosphorous tribromide (0.28 ml) was added to a solution of the product of step (ii) (1.55 g) in ether (20 ml) at 0 C., then stirred for 30 min. The reaction mixture was partitioned between ether and aqueous sodium hydrogen carbonate, the organics were separated then dried (MgSO4) and evaporated under reduced pressure. The residue was dissolved in DMF (20 ml) and sodium cyanide (0.5 g) was added. The mixture was stirred overnight then partitioned between ether and water; the organics were separated, washed with aqueous sodium hydrogen carbonate then dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography (eluent 1:1 ether/isohexane) to give the subtitle compound (0.53 g). 1H NMR CDCl3-d6: delta 6.91-6.9 (1H, m), 6.86-6.85 (1H, m), 6.77-6.76 (1H, m), 3.79 (3H, s), 3.69 (2H, s).
  • 3
  • [ 885270-32-6 ]
  • 2,4-dimethyl-N-(4-(2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)thiazol-2-yl)oxazole-5-carboxamide [ No CAS ]
  • N-(4-(1-(3-chloro-5-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)thiazol-2-yl)-2,4-dimethyloxazole-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% To a solution of 2,4-dimethyl-2-(4-(2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)thiazol-2-yl)oxazole-5-carboxamide (0.050 g, 0.136 mmol) in anhydrous dimethylformamide (3 mL) in a flamed dried flask under argon atmosphere at 0 C. was added sodium hydride (60% in mineral oil, 0.014 g, 0.339 mmol) was added in one portion. The reaction was stirred for 10 min at 0 C. then <strong>[885270-32-6]1-(bromomethyl)-3-chloro-5-methoxybenzene</strong> (0.034 g, 0.143 mmol) was added as a solid in one portion. The mixture was stirred for 90 minutes, then 1 hour at room temperature. After consumption of starting material, the reaction mixture was quenched with saturated ammonium chloride (25 mL) and extracted with ethyl acetate (2*25 mL). The combined organics were washed once with saturated sodium bicarbonate (50 mL) and dried over anhydrous sodium sulfate. The concentrated residue was purified by flash chromatography over silica gel using 95:5 dichloromethane/methanol to give N-(4-(4-(1-(3-chloro-5-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)thiazol-2-yl)-2,4-dimethyloxazole-5-carboxamide (0.068 g, 96%) as beige solid. 1H NMR (400 MHz, DMSO-d): delta 12.52 (s, 1H), 7.81 (d, 1H, J=2.0 Hz), 7.70 (dd, 1H, J=8.4, 1.6 Hz), 7.58 (s, 1H), 6.98 (d, 1H, J=8.4 Hz), 6.90 (m, 1H), 6.86 (m, 1H), 6.78 (m, 1H), 5.13 (bs, 2H), 3.74 (s, 3H), 3.01 (m, 2H), 2.75 (m, 2H), 2.48 (s, 3H), 2.40 (s, 3H). MS (ESI): Calcd. for C26H23ClN4O4S: 523, found 524 (M+1)+.
  • 4
  • [ 827614-64-2 ]
  • [ 885270-32-6 ]
  • 5-(3-chloro-5-methoxybenzyl)pyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In water; acetonitrile; at 80℃; for 1h; General procedure: A mixture of 1 -bromo-3-(bromomethyl)benzene(2.2 g, 8.87 mmol), 5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-2-amine (2.2 g, 10.0 mmol), [1 ,1 '-b/s(diphenylphosphino)ferrocene]dichloropalladium(ll)-dichloromethane complex (0.361 g, 0.44 mmol), potassium carbonate (2.45 g, 17.7 mmol), acetonitrile (80 ml_) and water (16 ml_) was stirred at 80 C under nitrogen for 2 h. The mixture was poured into water, extracted with ethyl acetate (150 ml_ x 2). The combined organic phase was concentrated. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate = 1 /1 ) to afford compound 5-(3-bromobenzyl)pyridin-2-amine (1 .6 g, 6.10 mmol, 68.8%) as a light-yellow oil.
  • 5
  • [ 885270-32-6 ]
  • N-(5-(3-chloro-5-methoxybenzyl)pyridin-2-yl)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide [ No CAS ]
  • 6
  • [ 885270-32-6 ]
  • N-(5-(3-chloro-5-methoxybenzyl)pyridin-2-yl)-1-methyl-6-oxo-1,4,5,6-tetrahydropyridazine-3-carboxamide [ No CAS ]
 

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