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Methyl 7-bromoquinoline-3-carboxylate

Methyl 7-bromoquinoline-3-carboxylate

Methyl 7-bromoquinoline-3-carboxylate

CAS No.: 1001756-23-5

Category Products

Cat.NO.:A142510 Purity:98%

Product Details of [ 1001756-23-5 ]

CAS No. :	1001756-23-5
Formula :	C₁₁H₈BrNO₂
M.W :	266.09
SMILES Code :	O=C(C1=CC2=CC=C(Br)C=C2N=C1)OC
MDL No. :	MFCD09834664
InChI Key :	GPLUSJRHUJLUHU-UHFFFAOYSA-N
Pubchem ID :	59321547

Safety of [ 1001756-23-5 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 1001756-23-5 ] Show Less

Physicochemical Properties

Num. heavy atoms	15
Num. arom. heavy atoms	10
Fraction Csp3	0.09
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	60.72
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	39.19 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.51
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.94
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.78
Log P_o/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.	2.32
Log P_o/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	2.96
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.7

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.7
Solubility	0.0527 mg/ml ; 0.000198 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.	-3.43
Solubility	0.1 mg/ml ; 0.000376 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	-4.63
Solubility	0.00622 mg/ml ; 0.0000234 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.	-5.84 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<0.0
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)	1.59

Application In Synthesis of [ 1001756-23-5 ]

* 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 [ 1001756-23-5 ]

[ 1001756-23-5 ] Synthesis Path-Downstream 1~14

1
[ 1020567-86-5 ]
[ 1001756-23-5 ]

Yield	Reaction Conditions	Operation in experiment
16%		2c) Methyl 7-bromo-3-quinolinecarboxylate A solution of 820 mg (1.93 mmol) of methyl (2E)-3-(4-bromophenyl)-2-([(4-methylphenyl)sulfonyl]amino}methyl)-2-propenoate, 995 mg (3.09 mmol) of bis(acetyloxy)(phenyl)-lambda3-iodane and 490 mg (1.93 mmol) of iodine in 35 mL of 1,2-dichloroethane were stirred at 70° C. for 30 min. The solvent was evaporated and the residue taken up in 25 mL DMF and 1.07 g (7.73 mmol) of K2CO3 was added. The mixture was stirred at 120° C. for 6 hr. EtOAc was added and the organics were washed with three portions of H2O then brine. The solution was then concentrated and the residue purified by silica gel chromatography (40 g of silica gel eluding with 0-40percent EtOAc in hexanes over 45 minutes) to give 80 mg (16percent) of methyl 7-bromo-3-quinolinecarboxylate as an off-white solid. 1H NMR (400 MHz, CDCl3): delta 9.34 (s, 1H), 8.81 (s, 1H), 8.35 (s, 1H), 7.80 (d, J=9 Hz, 1H), 7.73 (d, J=9 Hz, 1H), 4.02 (s, 3H). ESI-LCMS m/z 267 (M+H)+.

References: [1]Patent: US2008/96921,2008,A1 .Location in patent: Page/Page column 35.

2
[ 1001756-23-5 ]
[ 269409-70-3 ]
[ 1276656-22-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;palladium diacetate; triphenylphosphine; In 1,4-dioxane; water; at 60℃; for 1h;	2d) Methyl 7-[4-([3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-quinolinecarboxylate A solution of 78 mg (0.29 mmol) of <strong>[1001756-23-5]methyl 7-bromo-3-quinolinecarboxylate</strong>, 97 mg (0.44 mmol) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol, 3 mg (0.01 mmol) of palladium acetate, 8 mg (0.03 mmol) of triphenylphosphine, 218 mg (1.03 mmol) of K3PO4 and 25 muL of H2O in 1.0 mL of dioxane was stirred at 60° C. for 1 hr. EtOAc was added and the organics were washed with water and brine then concentrated. To the residue was added 65 mg (0.21 mmol) of 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole, 74 mg (0.54 mmol) of K2CO3 and 1.5 mL of DMF and the mixture was then stirred at 60° C. for 1 hr. EtOAc was added and the organics were washed with three portions of water, then brine. The solution was concentrated and the residue purified by silica gel chromatography (12 g of silica gel eluding with 0-40percent EtOAc in hexanes over 45 minutes) to give 47 mg (30percent) of methyl 7-[4-([3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-quinolinecarboxylate as a clear glass. 1H NMR (400 MHz, CDCl3): delta 9.44 (s, 1H), 8.83 (s, 1H), 8.28 (s, 1H), 7.96 (d, J=9 Hz, 1H), 7.82 (d, J=9 Hz, 1H), 7.64 (d, J=9 Hz, 2H), 7.41 (d, J=8 Hz, 2H), 7.35-7.31 (m, 1H), 6.92 (d, J=9 Hz, 2H), 4.79 (s, 2H), 4.02 (s, 3H), 3.38-3.34 (m, 1H), 1.45 (d, J=7 Hz, 6H). ESI-LCMS m/z 548 (M+H)+.
	With potassium phosphate; palladium diacetate; triphenylphosphine; In 1,4-dioxane; water; at 60℃; for 1h;	A solution of <strong>[1001756-23-5]methyl 7-bromo-3-quinolinecarboxylate</strong> 2c (78 mg, 0.29 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol 3b (97 mg, 0.44 mmol), palladium(II) acetate (3 mg, 0.01 mmol), triphenylphosphine (8 mg, 0.03 mmol), potassium phosphate (218 mg, 1.03 mmol), and water (25 muL) in dioxane (1.0 mL) was stirred at 60 °C for 1 hour. Ethyl acetate was added and the organics were washed with water and brine, and then concentrated to give methyl 7-(4-hydroxyphenyl)quinoline-3-carboxylate 4c. To methyl 7-(4-hydroxyphenyl)quinoline-3-carboxylate 4c was added 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole 5a (65 mg, 0.21 mmol), potassium carbonate (74 mg, 0.54 mmol) and N,N-dimethylformamide (1.5 mL) and the mixture was then stirred at 60 °C for 1 hour. Ethyl acetate was added and the organics were washed with three portions of water, then brine. The solution was concentrated, and the residue was purified by silica gel chromatography (hexanes to 2:3 ethyl acetate:hexanes) to give methyl 7-[4-([3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-quinolinecarboxylate (47 mg, 30percent) as a clear glass (1H NMR (400 MHz, CDCl3): 9.44 (s, 1H), 8.83 (s, 1H), 8.28 (s, 1H), 7.96 (d, J = 9 Hz, 1H), 7.82 (d, J = 9 Hz, 1H), 7.64 (d, J = 9 Hz, 2H), 7.41 (d, J = 8 Hz, 2H), 7.35-7.31 (m, 1H), 6.92 (d, J = 9 Hz, 2H), 4.79 (s, 2H), 4.02 (s, 3H), 3.38-3.34 (m, 1H), 1.45 (d, J = 7 Hz, 6H); ESI-LCMS m/z 548 (M+H)). To methyl 7-[4-([3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-quinolinecarboxylate (47 mg, 0.09 mmol) in a mixture of ethanol (3 mL), tetrahydrofuran (1 mL), and water (1 mL) was added sodium hydroxide (35 mg, 0.86 mmol) and the mixture stirred at 50 °C for 16 hours. The mixture was concentrated to 1/3 volume then added dropwise to a stirred solution of 0.5 N hydrochloric acid (10 mL). The resulting solids were collected by suction filtration, washed with water, then dried to yield 7-[4-([3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-quinolinecarboxylic acid 1e (32 mg, 70percent) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): delta 9.30 (s, 1H), 8.97 (s, 1H), 8.24-8.21 (m, 2H), 7.99 (d, J = 8 Hz, 1H), 7.76 (d, J = 8 Hz, 2H), 7.63-7.61 (m, 2H), 7.55-7.52 (m, 1H), 6.93 (d, J = 9 Hz, 2H), 4.88 (s, 2H), 3.50-3.44 (septet, J = 7 Hz, 1H), 1.33 (d, J = 7 Hz, 6H); ESI-LCMS m/z 534 (M+H).

References: [1]Patent: US2008/96921,2008,A1 .Location in patent: Page/Page column 35-36.
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1206 – 1213.

3
[ 1001756-23-5 ]
[ 1020567-95-6 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1206 – 1213.

4
[ 1001756-23-5 ]
[ 1020567-77-4 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1206 – 1213.

5
[ 3132-99-8 ]
[ 1001756-23-5 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 188 – 193.

6
[ 500163-43-9 ]
[ 1001756-23-5 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 188 – 193.

7
methyl 2-(acetoxy-(3-bromophenyl)methyl)acrylate [ No CAS ]
[ 1001756-23-5 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 188 – 193.

8
[ 1416560-86-5 ]
[ 1001756-23-5 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 188 – 193.

9
[ 1001756-23-5 ]
[ 1416560-88-7 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 188 – 193.

10
[ 1001756-23-5 ]
[ 1416560-89-8 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 188 – 193.

11
[ 1001756-23-5 ]
[ 1416560-90-1 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 188 – 193.

12
[ 1001756-23-5 ]
C₁₄H₁₃N₃O [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 188 – 193.

13
[ 1001756-23-5 ]
C₅₆H₆₅N₉O₁₁S [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 188 – 193.

14
[ 1001756-23-5 ]
[ 1066-54-2 ]
[ 1416560-87-6 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 188 – 193.

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