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Chemical Structure| 1070879-27-4 Chemical Structure| 1070879-27-4

Structure of 1070879-27-4

Chemical Structure| 1070879-27-4

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Product Details of [ 1070879-27-4 ]

CAS No. :1070879-27-4
Formula : C10H8BrNO
M.W : 238.08
SMILES Code : COC1=CC=C2C(Br)=CC=NC2=C1
MDL No. :MFCD08063187
InChI Key :HSLGTRSMCWHZQH-UHFFFAOYSA-N
Pubchem ID :21568292

Safety of [ 1070879-27-4 ]

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

Computational Chemistry of [ 1070879-27-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 10
Fraction Csp3 0.1
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 55.94
TPSA ?

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

22.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.33
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

2.98
Log Po/w (WLOGP)?

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

3.01
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.

2.19
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

3.1
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.72

Water Solubility

Log S (ESOL):?

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

-3.7
Solubility 0.0479 mg/ml ; 0.000201 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.

-3.11
Solubility 0.186 mg/ml ; 0.00078 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

-4.69
Solubility 0.00489 mg/ml ; 0.0000206 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

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.

-5.64 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)

1.66

Application In Synthesis of [ 1070879-27-4 ]

* 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 [ 1070879-27-4 ]

[ 1070879-27-4 ] Synthesis Path-Downstream   1~12

  • 1
  • [ 1070879-27-4 ]
  • [ 594-27-4 ]
  • [ 6238-12-6 ]
YieldReaction ConditionsOperation in experiment
With triphenylphosphine; lithium chloride;bis-triphenylphosphine-palladium(II) chloride; In DMF (N,N-dimethyl-formamide); at 20 - 120℃; for 16h; 4 g of triphenylphosphine, 5.3 g of lithium chloride, 14 ml of tetramethyltin and 2.1 g of bis(triphenylphosphine)palladium(II) chloride are added to a solution of 6 g of <strong>[1070879-27-4]4-bromo-7-methoxyquinoline</strong> in 100 ml of DMF, under an inert atmosphere of argon at a temperature in the region of 20° C. The reaction medium is heated at a temperature in the region of 120° C. for 16 hours. After cooling, the insoluble material is filtered off. The filtrate is concentrated under reduced pressure. The residue obtained is taken up in 300 ml of EtOAc and 300 ml of water. After separation of the phases by settling, the organic phase is dried over magnesium sulfate, filtered and then concentrated under reduced pressure. The oil obtained is taken up in 300 ml of EtOAc and 300 ml of water and then acidified with hydrochloric acid to pH 1. The aqueous phase is basified with sodium hydroxide to pH 10 and then extracted with 300 ml of EtOAc. After separation of the phases by settling, the organic phase is dried over magnesium sulfate, filtered and then concentrated under reduced pressure to give 2.7 g of 4-methyl-7-methoxyquinoline, the characteristics of which product are as follows: 1H NMR spectrum (300 z, (CD3)2SO d6, delta in ppm): 2.65 (s: 3H); 3.94 (s: 3H); 7.23 (broad d, J=4.5 Hz: 1H); 7.28 (dd, J=9 and 3 Hz: 1H); 7.40 (d, J=3 Hz: 1H); 8.01 (d, J=9 Hz: 1H); 8.58 (d, J=4.5 Hz: 1H). Mass IE m/z=173 M+. base peak m/z=158 (M-CH3)+ m/z=143 (M-CH2O)+. m/z=130 (m/z=158-CO)+
  • 2
  • [ 82121-05-9 ]
  • [ 1070879-27-4 ]
YieldReaction ConditionsOperation in experiment
72% With phosphorus(V) oxybromide; at 110℃; General procedure: According to Scheme C,7-Methoxyquinolin-4-ol (1 eq) and POBr3 (10.4 eq.) Were placed in a round bottom flask,And the mixture was stirred for 3 hours. After completion of the reaction, the reaction solution was slowly added to the ice water and basified to pH 8 or more with ammonia water.The organic layer was extracted three times with ethyl acetate from the mixture of water and solution, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained mixture was subjected to column chromatography to give 4-bromo-7-methoxyquinoline. (1 eq.), 2-benzyl-4,4,5,5-tetramethyl-l, 3,2-dioxaborolane (1.2 eq.), Potassium carbonate (3 eq.), Tetrakis Phosphine) palladium (0) (0.05 eq.) Was stirred at 100 for 6 h under a solution of 1,4-dioxane and water in a ratio of 4: 1. After cooling to room temperature, the mixture was extracted three times with ethyl acetate, dried over anhydrous magnesium sulfate and filtered, and then concentrated under reduced pressure. Subsequently, a 4-benzylquinoline compound was obtained by column chromatography.
With phosphorus(V) oxybromide; at 110℃; for 3.0h; 22.74 g of 4-hydroxy-7-methoxyquinoline are added to 200 g of phosphorus oxybromide preheated to a temperature in the region of 110 C. The reaction medium is heated at this same temperature for 3 hours. The reaction medium is poured, while hot, into a mixture of 500 ml of EtOAc and 500 ml of ice-cold water. The medium is neutralized with potassium carbonate to pH 7. After separation of the phases by settling, the organic phase is dried over magnesium sulfate, evaporated under reduced pressure and then purified by column chromatography (SiO2, EtOAc/cyclohexane 50/50 by volume as eluents, Ar), and 14.6 g of the expected product are obtained. [1475] 1H NMR spectrum (300 MHz, (CD3)2SO d6, delta in ppm): 3.97 (s: 3H); 7.43 (dd, J=9 and 3 Hz: 1H); 7.49 (d, J=3 Hz: 1H); 7.79 (d, J=4.5 Hz: 1H); 8.06 (d, J=9 Hz: 1H); 8.67 (d, J=4.5 Hz: 1H). [1476] Mass IE m/z=237 M+. base peak [1477] 4-Hydroxy-7-methoxyquinoline is prepared according to the process described in: J. Am. Chem. Soc., 68, 1268, 1946.
YieldReaction ConditionsOperation in experiment
Exemplary of the 4-bromoquinoline compounds are: 4-bromoquinoline; 4-bromo-6-methoxyquinoline; 4-bromo-6-methylquinoline; 4-bromo-7-methoxyquinoline; 4-bromo-6,7-dimethoxyquinoline; 4-bromo-6,7-methylenedioxyquinoline; ...
  • 4
  • [ 1070879-27-4 ]
  • 4-benzyl-7-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)quinoline trifluoroacetate [ No CAS ]
  • 5
  • [ 1070879-27-4 ]
  • 4-benzylquinolin-7-yl trifluoromethanesulfonate [ No CAS ]
  • 6
  • [ 1070879-27-4 ]
  • 4-benzylquinolin-7-ol [ No CAS ]
  • 7
  • [ 1070879-27-4 ]
  • tert-butyl 4-[4-(4-benzylquinolin-7-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate [ No CAS ]
  • 8
  • [ 1070879-27-4 ]
  • [ 87100-28-5 ]
  • 4-benzyl-7-methoxyquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; General procedure: According to Scheme C,7-Methoxyquinolin-4-ol (1 eq) and POBr3 (10.4 eq.) Were placed in a round bottom flask,And the mixture was stirred for 3 hours. After completion of the reaction, the reaction solution was slowly added to the ice water and basified to pH 8 or more with ammonia water.The organic layer was extracted three times with ethyl acetate from the mixture of water and solution, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained mixture was subjected to column chromatography to give <strong>[1070879-27-4]4-bromo-7-methoxyquinoline</strong>. (1 eq.), 2-benzyl-4,4,5,5-tetramethyl-1, 3,2-dioxaborolane (1.2 eq.), Potassium carbonate (3 eq.), Tetrakis Phosphine) palladium (0) (0.05 eq.) Was stirred at 100 C for 6 h under a solution of 1,4-dioxane and water in a ratio of 4: 1. After cooling to room temperature, the mixture was extracted three times with ethyl acetate, dried over anhydrous magnesium sulfate and filtered, and then concentrated under reduced pressure. Subsequently, a 4-benzylquinoline compound was obtained by column chromatography.
  • 9
  • [ 1070879-27-4 ]
  • 4-benzyl-7-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)quinoline [ No CAS ]
  • 10
  • [ 1070879-27-4 ]
  • 4-(4-methoxyl-3-methylbenzyl)-7-methoxylquinoline [ No CAS ]
  • 11
  • [ 1070879-27-4 ]
  • 4-(4-hydroxyl-3-methylbenzyl)-7-hydroxylquinoline [ No CAS ]
  • 12
  • [ 1070879-27-4 ]
  • [ 32723-67-4 ]
  • 4-[hydroxy-(7-methoxylquinolin-4-yl)methyl]-2-methylanisole [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% (0640) <strong>[1070879-27-4]4-bromo-7-methoxyquinoline</strong> (204 mg, 0.86 mmol) was dissolved in anhydrous THF in -78C, n- butyl lithium was added slowly. The reaction mixture was stirred at -78C for 2h, and then 3-methyl-4-anisaldehyde (257 mg, 1.72 mmol) was added slowly, the mixture was slowly warmed to room temperature and stirred overnight. The mixture was then diluted with water and extracted with ethyl acetate. The organic phase was dried and concentrated. The crude product was purified by flash chromatography (dichloromethane / ethyl acetate 0-10%) to yield product as a yellow solid (243 mg, 91% yield). ESI-MS m/z: 310.1444 [M+H]+; Punty: 99.6%. 1H NMR (400 MHz, chlorofornw/) delta 8.89 (d, J= 4.5 Hz, 1H), 7.77 (d, J = 9.3 Hz, 1H), 7.63 (dd, J = 4.5, 0.9 Hz, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.15- 7.02 (m, 3H), 6.75 (d, J = 9.0 Hz, lH), 6.39 (s, 1H), 3.92 (s, 3H), 3.79 (s, 3H), 2.16 (s, 3H). 13C NMR (101 MHz, CDCI3) delta 160.05, 157.80, 150.33, 148.58, 133.87, 129.80, 126.07, 125.09, 120.63, 119.78, 1 16.29, 110.08, 72.69, 55.64, 55.48, 16.48.
 

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Technical Information

Categories

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[ 1070879-27-4 ]

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