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Chemical Structure| 70049-46-6 Chemical Structure| 70049-46-6

Structure of 70049-46-6

Chemical Structure| 70049-46-6

2,4-Dichloro-6-methoxyquinoline

CAS No.: 70049-46-6

4.5 *For Research Use Only !

Cat. No.: A446998 Purity: 98%

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Product Details of [ 70049-46-6 ]

CAS No. :70049-46-6
Formula : C10H7Cl2NO
M.W : 228.08
SMILES Code : COC1=CC=C2N=C(Cl)C=C(Cl)C2=C1
MDL No. :MFCD03285967
InChI Key :FUAYQQYYACASFP-UHFFFAOYSA-N
Pubchem ID :948356

Safety of [ 70049-46-6 ]

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

Computational Chemistry of [ 70049-46-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
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 58.26
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.

2.63
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

3.75
Log Po/w (WLOGP)?

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

3.55
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.

2.6
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

3.68
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.24

Water Solubility

Log S (ESOL):?

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

-4.08
Solubility 0.019 mg/ml ; 0.0000833 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.

-3.91
Solubility 0.0282 mg/ml ; 0.000124 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

-5.07
Solubility 0.00195 mg/ml ; 0.00000855 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

Yes
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.

-5.03 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

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<2.0
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 [ 70049-46-6 ]

* 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 [ 70049-46-6 ]

[ 70049-46-6 ] Synthesis Path-Downstream   1~30

  • 1
  • [ 151772-24-6 ]
  • [ 70049-46-6 ]
  • 2
  • 2,4-Dichloro-6-methoxy-quinoline-3-carboxylic acid [ No CAS ]
  • [ 70049-46-6 ]
  • 3
  • [ 141-82-2 ]
  • [ 104-94-9 ]
  • [ 70049-46-6 ]
YieldReaction ConditionsOperation in experiment
35% With trichlorophosphate; at 20℃; for 5.25h;Reflux; 2,4-DICHLORO-6-METHOXYQUINOLINE. Phosphorus(V)oxychloride (40 mL, 1.5 M) was added through a condenser into a 3-neck round bottom flask containing malonic acid (6.244 g, 60.00 mmol) and a stir bar at room temperature. While stirring, p-anisidine (9.236 g, 75.00 mmol) was added in small portions over a period of 15 minutes through an open neck of the round bottom flask. The reaction mixture was heated and stirred at reflux for 5 hours. The reaction mixture was allowed to cool to room temperature before it was poured over crushed ice (700 mL). The pH of the resulting aqueous solution was then adjusted to 10 with concentrated ammonium hydroxide (85 mL). The aqueous suspension was extracted with dichloromethane. The combined organic layers were then dried over MgSO4 before concentration. Purification by column chromatography (0-5percent ethyl acetate in hexanes) yielded the title compound as a slightly yellow solid (4.7812 g, 35percent). Mp 170.5-171.5° C.; Rf=0.27 (2percent EtOAc/hexanes); IR (film) 3084, 3013, 2982, 1623, 1562, 1499 cm-1; 1H NMR (500 MHz, CDCl3) delta 7.90 (d, J=9.0 Hz, 1H), 7.45 (s, 1H), 7.40 (dd, J=9.0, 3.0 Hz, 1H), 7.36 (d, J=3.0 Hz, 1H), 3.96 (s, 3H); 13C NMR (125 MHz, CDCl3) ppm 158.9, 147.0, 144.0, 142.6, 130.4 126.3, 124.1, 122.0, 101.9, 55.7; HRMS submitted.
19% A mixture of p- anisidine (100 g, 0.813 mol), and malonic acid (85.0 g, 0.817 mol) in POCI3 (500 mL) was refluxed for 6 hours. The excess POCI3 was removed in vacuo and the residue was neutralized with 8 M NaOH to pH 7. The aqueous layer was extracted with CH2CI2 (300 mL x 3), washed with brine (500 mL), dried over Na2S04 and concentrated under reduced pressure. Purification by column chromatography on silica gel (PE / EtOAc = 15/1) gave desired (35.0 g, yield: 19percent).
With trichlorophosphate; at 20 - 105℃; for 3.25h; POC13 (80 ml) was added through a condenser into a 250 mL round bottom flask containing malonic acid (25.3 g, 244 mmol) at 20 °C. While stirring, 4-methoxyaniline (20 g, 162 mmol) was added in small portions over a period of 15 minutes. The reaction mixture was heated and stirred at 105 °C for 3 h. Thenthe reaction mixture was cooled to 20 °C and concentrated in vacuo to remove POC13. The resulting residue was dissolved in DCM (200 mL). Then the mixture was poured into concentrated ammonium hydroxide and the final pH of the aquesous layer was about 10. The aqueous layer was extracted with DCM (3 x 100 mL). The combined organic layers were dried over Na2504, filtered and concentrated in vacuo. The resulting residue was purified by columnchromatography (5i02, PE:EtOAc =100:1 to 10:1) to give the title compound.
  • 4
  • [ 68-12-2 ]
  • [ 70049-46-6 ]
  • [ 151772-24-6 ]
  • 6
  • [ 70049-46-6 ]
  • [ 419566-57-7 ]
  • 7
  • [ 70049-46-6 ]
  • [ 419566-62-4 ]
  • 8
  • [ 70049-46-6 ]
  • 2-methoxy-8,9,10,11-tetrahydro-5<i>H</i>-dibenzo[<i>b</i>,<i>h</i>][1,6]naphthyridin-6-one [ No CAS ]
  • 9
  • [ 110-91-8 ]
  • [ 70049-46-6 ]
  • [ 952443-70-8 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In ethylene glycol; at 145℃; for 1.25h;Microwave reaction; (1) A mixture of <strong>[70049-46-6]2,4-dichloro-<strong>[70049-46-6]6-methoxyquinoline</strong></strong> (0.228 g), morpholine (262 muL), N,N-diisopropylethylamine (348 muL), and ethylene glycol (4 mL) was heated with microwave (145°C) for 75 min with stirring. The reaction mixture was cooled to room temperature, followed by addition of water, the mixture was extracted with chloroform and washed with saturated brine, and the organic layer was dried with anhydrous sodium sulfate. The desiccant was removed by filtration, the residue concentrated under reduced pressure was purified by silica gel column chromatography (chloroform/hexane = 1/1) to obtain 2-chloro-6-methoxy-4-morpholinoquinoline (0.182 g).
  • 10
  • [ 67-56-1 ]
  • [ 124-41-4 ]
  • [ 70049-46-6 ]
  • [ 952435-01-7 ]
YieldReaction ConditionsOperation in experiment
at 70℃; for 3h; Reference Example 10: Synthesis of 2-chloro-4,6-dimethoxyquinoline To a solution of <strong>[70049-46-6]2,4-dichloro-<strong>[70049-46-6]6-methoxyquinoline</strong></strong> (0.97 g) synthesised from p-anisidine and malonic acid according to the method of in methanol (20 mL) was added sodium methoxide (1.37 g), and the mixture was stirred at 70°C for 3 h. The reaction solution was added dropwise to ice water, and the resulting solids were collected by filtration. The resulting solids were purified by silica gel column chromatography (hexane/ethyl acetate = 5:1) to obtain 2-chloro-4,6-dimethoxyquinoline (0.61 g) as white solids. LC/MS: ESI+ (m/z) 224 (M++1) 1H-NMR (300 MHz, CDCl3): delta7.83 (d, J=9.0 Hz, 1H),7.36 (d, J=2.7 Hz, 1H), 7.33 (dd, J=2.7 Hz, J=9.0 Hz, 1H), 4.04 (s, 3H), 3.91 (s, 3H) The following compounds were synthesised by the same method.
  • 11
  • [ 20439-47-8 ]
  • [ 70049-46-6 ]
  • [ 1353892-00-8 ]
YieldReaction ConditionsOperation in experiment
77% With sodium t-butanolate;2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; bis(dibenzylideneacetone)-palladium(0); In alpha,alpha,alpha-trifluorotoluene; at 120℃; for 0.166667h;Microwave irradiation; H,4CL6MEOQUIN-BAM. A 2-5 mL muW vial was charged with (R,R)-diaminocyclohexane (125.2 mg, 1.096 mmol), <strong>[70049-46-6]2,4-dichloro-<strong>[70049-46-6]6-methoxyquinoline</strong></strong> (500 mg, 2.190 mmol), Pd(dba)2 (12.6 mg, 22.0 mumol), rac-BINAP (13.6 mg, 22.0 mumol), and sodium tert-butoxide (316.2 mg, 3.290 mmol). See Wagaw et al., 1997, which is incorporated herein by reference. Trifluoromethylbenzene (3.8 mL) was added and the resulting suspension was heated at 120° C. and stirred in the microwave for 10 min. The reaction mixture was triturated with CH2Cl2 and filtered. The filtrate was concentrated and purified by column chromatography (10-20percent ethyl acetate in hexanes) to provide a yellow solid (420.3 mg, 77percent) that was pure by 1H NMR; [alpha]D20 +610 (c 0.18, CHCl3); Rf=0.18 (20percent EtOAc/hexanes); IR (film) 3218, 2925, 1605, 1495 cm-1; 1H NMR (600 MHz, CDCl3, 325 K) delta 7.64 (d, J=9.0 Hz, 2H), 7.30 (d, J=3.0 Hz, 2H), 7.25 (dd, J=9.0, 3.0 Hz, 2H), 6.38 (br s, 2H), 5.72 (br s, 2H), 4.05-3.90 (m, 2H), 3.91 (s, 6H), 2.39-2.25 (m, 2H), 1.90-1.80 (m, 2H), 1.55-1.35 (m, 4H); 13C NMR (150 MHz, CDCl3, 325 K) ppm 155.5, 155.4, 144.0, 141.4, 127.6, 121.9, 121.8, 111.8, 103.7, 56.1, 55.6, 33.0, 24.9; HRMS (ESI): Exact mass calcd for C26H27Cl2N4O2 [M+H]+ 497.1511. found 497.1500.
  • 12
  • [ 70049-46-6 ]
  • [ 1353891-43-6 ]
  • 13
  • [ 141-82-2 ]
  • [ 90-04-0 ]
  • [ 70049-46-6 ]
YieldReaction ConditionsOperation in experiment
19% A mixture of p- anisidine (100 g, 0.813 mol), and malonic acid (85.0 g, 0.817 mol) in POCl3 (500 mL) was refluxed for 6 hours. The excess POCl3 was removed in vacuo and the residue was neutralized with 8 M NaOH to pH 7. The aqueous layer was extracted with CH2CI2 (300 mL x 3), washed with brine (500 mL), dried over Na2S04 and concentrated in vacuo.Purification by column chromatography on silica gel (PE / EtOAc = 15/1) gave the desired product (35.0 g, yield: 19percent).
  • 14
  • [ 70049-46-6 ]
  • [ 1371588-86-1 ]
  • 15
  • [ 70049-46-6 ]
  • [ 1371588-03-2 ]
  • 16
  • [ 70049-46-6 ]
  • [ 1371588-93-0 ]
  • 17
  • [ 70049-46-6 ]
  • [ 1371588-06-5 ]
  • 18
  • [ 70049-46-6 ]
  • [ 1371589-25-1 ]
  • 19
  • [ 70049-46-6 ]
  • [ 1371589-24-0 ]
YieldReaction ConditionsOperation in experiment
55% With ammonia; In methanol; at 150℃; for 16h;sealed tube; A suspension of 2,4-dichloro-6- methoxyquinoline (5.00 g, 22.0 mmol) in NH3 (g) / MeOH (saturated, 40 mL) was heated to 150 °C for 16 hours in a sealed tube. The solvent was removed in vacuo and the residue was diluted with MeOH (20 mL). The mixture was filtered off and the filtrate was concentrated to give the crude product, which was purified by column chromatography on silica gel (PE / EtOAc = 2/1) to give 2-chloro-6-methoxyquinolin-4-amine (7.50 g, yield: 55percent) as a yellow solid.
55% With ammonia; In methanol; at 150℃; for 16h;sealed tube; A suspension of <strong>[70049-46-6]2,4-dichloro-<strong>[70049-46-6]6-methoxyquinoline</strong></strong> (5.00 g, 22.0 mmol) in NH3 (g) / MeOH (saturated, 40 mL) was heated to 150 °C for 16 hours in a sealed tube. The solvent was removed and the residue was diluted with MeOH (20 mL). The mixture was filtered off and the filtrate was concentrated to give the crude product. Purification by column chromatography on silica gel (PE / EtOAc = 2/1) gave product (7.50 g, yield: 55percent) as a solid
  • 20
  • [ 70049-46-6 ]
  • [ 294653-58-0 ]
  • [ 1386328-64-8 ]
  • 21
  • [ 80-05-7 ]
  • [ 70049-46-6 ]
  • [ 1417625-38-7 ]
  • 22
  • [ 124-41-4 ]
  • [ 70049-46-6 ]
  • [ 952435-01-7 ]
  • 23
  • [ 70049-46-6 ]
  • [ 156304-06-2 ]
  • [ 1424371-19-6 ]
  • 25
  • [ 70049-46-6 ]
  • [ 878380-77-9 ]
  • 28
  • [ 70049-46-6 ]
  • 6-methoxy-4-[(4-methylphenyl)sulfonyl]quinolin-2(1H)-one [ No CAS ]
  • 29
  • [ 70049-46-6 ]
  • 6-methoxy-2-oxo-1,2-dihydroquinoline-4-carbonitrile [ No CAS ]
 

Historical Records

Technical Information

Categories

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[ 70049-46-6 ]

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[ 70049-46-6 ]

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