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Chemical Structure| 26218-75-7 Chemical Structure| 26218-75-7

Structure of Methyl 6-bromopicolinate
CAS No.: 26218-75-7

Chemical Structure| 26218-75-7

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Product Details of [ 26218-75-7 ]

CAS No. :26218-75-7
Formula : C7H6BrNO2
M.W : 216.03
SMILES Code : COC(C1=CC=CC(=N1)Br)=O
MDL No. :MFCD06203934
InChI Key :SGNCOKUHMXLGAH-UHFFFAOYSA-N
Pubchem ID :16217886

Safety of [ 26218-75-7 ]

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

Computational Chemistry of [ 26218-75-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 43.22
TPSA ?

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

39.19 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.92
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

2.06
Log Po/w (WLOGP)?

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

1.63
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.

1.09
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

1.87
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.71

Water Solubility

Log S (ESOL):?

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

-2.75
Solubility 0.385 mg/ml ; 0.00178 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.

-2.51
Solubility 0.665 mg/ml ; 0.00308 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

-2.96
Solubility 0.237 mg/ml ; 0.0011 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.

-6.16 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<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)

1.85

Application In Synthesis of [ 26218-75-7 ]

* 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 [ 26218-75-7 ]

[ 26218-75-7 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 917-64-6 ]
  • [ 26218-75-7 ]
  • [ 638218-78-7 ]
YieldReaction ConditionsOperation in experiment
100% In diethyl ether; at 20℃; for 0.5h;Inert atmosphere; Dissolve methyl 6-bromopicolinate (Int-1-a) (5 g, 23.1 mmol) in diethyl ether (100 mL),Methyl magnesium iodide (17 mL, 50.8 mmol) was added under a nitrogen atmosphere, and the mixture was stirred at room temperature for 0.5 hours.Water and 2N hydrochloric acid were added to the reaction solution, and extracted three times with ethyl acetate.The organic layers were combined and washed successively with a saturated aqueous sodium hydrogen carbonate solution and a saturated saline solution.It was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain the title compound (5 g, yield: 100%) in this step.
85% In diethyl ether; at 20℃; for 0.0833333h;Inert atmosphere; Methylmagnesium iodide (3M in Et20, 1.50 ml, 4.48 mmol) was added to a solution of methyl 6-bromopyridine-2- carboxylate (0.430 g, 1.99 mmol) in dry Et20 (1 5 ml) under N2. After 5 min at RT the reaction was quenched with 1 M HCI (10 ml) and extracted with EtOAc (15 ml). The organic extract was washed with sat. NaHC03 solution (1 5 ml) and brine (10 ml), dried (MgS04) and concentrated in vacuo. The desired product was obtained as a yellow oil (0.365 g, 1.69 mmol, 85%). Rf 0.60 (1 :1 Hexane:EtOAc); I R (cm-1 ) 3420, 2975, 2930, 1731 , 1701 , 1 580, 1 553; 1 H NMR (400 MHz, DMSO-d6) 1.42 (6H, s, C(CH2)2), 5.33 (1 H, s, OH), 7.47 (1 H, dd, J = 7.7, 0.9 Hz, H-5), 7.67 (1 H, dd, J = 7.7, 0.9 Hz, H-3), 7.73 (1 H, dd, J = 7.7, 7.7 Hz, H-4); 13C N MR (125 MHz, DMSO-d6) 30.9 (C(CH2)2), 72.6 (C(CH2)2), 1 18.5 (Ar-C), 126.0 (Ar-C), 140.4 (Ar-C), 140.5 (Ar-C), 170.8 (Ar-C).
85% In diethyl ether; at 20℃; for 0.0833333h;Inert atmosphere; (0223) Synthesis of 2-(6-bromopyridin-2-yl)propan-2-ol. Methylmagnesium iodide (3M in Et20, 1.50 ml, 4.48 mmol) was added to a solution of methyl 6-bromopyridine-2- carboxylate (0.430 g, 1.99 mmol) in dry Et20 (15 ml) under N2. After 5 min at RT the reaction was quenched with 1 M HCI (10 ml) and extracted with EtOAc (15 ml). The organic extract was washed with sat. NaHC03 solution (15 ml) and brine (10 ml), dried (MgS04) and concentrated in vacuo. The desired product was obtained as a yellow oil (0.365 g,1.69 mmol, 85%). Rf 0.60 (1 :1Hexane:EtOAc); IR (cm 1) 3420, 2975, 2930, 1731, 1701, 1580, 1553; 1H NMR (400 MHz, DMSO-d6) 1.42 (6H, s, C(CH2)2), 5.33 (1H, s, OH), 7.47 (1H, dd, J = 7.7, 0.9 Hz, H-5), 7.67 (1H, dd, J = 7.7, 0.9 Hz, H-3), 7.73 (1H, dd, J = 7.7, 7.7 Hz, H-4); 13C NMR (100 MHz, DMSO- 6) 30.9 (C(CH2)2), 72.6 (C(CH2)2), 1 18.5 (Ar-C), 126.0 (Ar-C), 140.4 (Ar-C), 140.5 (Ar-C), 170.8 (Ar-C).
With hydrogenchloride; In diethyl ether; water; 1) Production of 2-(6-bromo-2-pyridinyl)-2-propanol In a nitrogen atmosphere, 30 mL of 3 M methylmagnesium iodide/diethyl ether was added to 300 mL of diethyl ether solution of 8.72 g of methyl 6-bromopyridine-2-carboxylate. Water and 2 N hydrochloric acid were added to the reaction liquid, and extracted with ethyl acetate. This was washed with aqueous saturated sodium hydrogencarbonate solution and saturated saline water, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure to obtain 8.51 g of crude 2-(6-bromo-2-pyridinyl)-2-propanol as a yellow oily substance. 1H-NMR (400 MHz, CDCl3) delta: 7.56 (1H, t, J=7.8 Hz), 7.38 (1H, dd, J=7.8, 1.0 Hz), 7.36 (1H, dd, J=7.8, 1.0 Hz), 1.55(6H, s). ESI-MS Found: m/z[M+H]+ 216, 218.
Reference Example 2:Production of 2-allyl-l -[6-(I -hydroxy- 1 -methyl ethyl)pyridin-2-yl] -6-{ [4-(4-methylpiperazin- 1- yl)phenyl]ammo>-l,2-dihvdro-3H-pyrazolo[3,4-dlpyrimidin-3-one1) Production of 2-(6-bromo-2-pyridinyl)-2-propanol:In a nitrogen atmosphere, 30 mL of 3 M methylmagnesium iodide/diethyl ether was added to 300 mL of diethyl ether solution of 8.72 g of methyl 6-bromopyridine-2- carboxylate. Water and 2 N hydrochloric acid were added to the reaction liquid, and extracted with ethyl acetate. This was washed with aqueous saturated sodium hydrogencarbonate solution and saturated saline water, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure to obtain 8.51 g of crude 2-(6-bromo-2-pyridinyl)-2- propanol as a yellow oily substance. iH-NMR (400 MHz, CDC13) 6: 7.56 (IH, t, J=7.8 Hz), 7.38 (IH, dd, J=7.8, 1.0 Hz), 7.36 (IH, dd, J=7.8, 1.0 Hz), 1.55(6H, s). ESI-MS Found: m/z[M+H]+ 216, 218.
In a nitrogen atmosphere, 30 mL of 3 M methylmagnesium iodide/diethyl ether was added to 300 mL of diethyl ether solution of 8.72 g of methyl 6-bromopyridine-2- carboxylate. Water and 2N hydrochloric acid were added to the reaction liquid, and extracted with ethyl acetate. This was washed with aqueous saturated sodium hydrogencarbonate solution and saturated saline water, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure to obtain 8.51 g of crude 2-(6-bromo-2-pyridinyl)-2- propanol as a yellow oily substance. iH-NMR (400 MHz, CDC13) delta: 7.56 (IH, t, J=7.8 Hz), 7.38 (IH, dd, J=7.8, 1.0 Hz), 7.36 (IH, dd, J=7.8, 1.0 Hz), 1.55(6H, s). ESI-MS Found: m/z[M+H]+ 216, 218.
With hydrogenchloride; In diethyl ether; water;Inert atmosphere; Step 1) Production of 2-(6-bromo-2-pyridinyl)-2-propanol: In a nitrogen atmosphere, 30 mL of 3 M methylmagnesium iodide/diethyl ether was added to 300 mL of diethyl ether solution of 8.72 g of methyl 6-bromopyridine-2- carboxylate. Water and 2 N hydrochloric acid were added to the reaction liquid, and extracted with ethyl acetate. This was washed with aqueous saturated sodium hydrogencarbonate solution and saturated saline water, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure to obtain 8.51 g of crude 2-(6-bromo-2-pyridinyl)-2- propanol as a yellow oily substance. iH-NMR (400 MHz, CDC13) delta: 7.56 (1H, t, J=7.8 Hz), 7.38 (1H, dd, J=7.8, 1.0 Hz), 7.36 (1H, dd, J=7.8, 1.0 Hz), 1.55(6H, s). ESI-MS Found: m/z[M+H]+ 216, 218.
In diethyl ether;Inert atmosphere; In a nitrogen atmosphere, 30 mL of 3 M methylmagnesium iodide/diethyl ether was added to 300 mL of diethyl ether solution of 8.72 g of methyl 6-bromopyridine-2-carboxylate. Water and 2 N hydrochloric acid were added to the reaction liquid, and extracted with ethyl acetate. This was washed with aqueous saturated sodium hydrogencarbonate solution and saturated saline water, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure to obtain crude 2-(6-bromo-2-pyridinyl)-2-propanol as a yellow oily substance. 1H-NMR (400 MHz, CDCl3) delta: 7.56 (1H, t, J=7.8 Hz), 7.38 (1H, dd, J=7.8, 1.0 Hz), 7.36 (1H, dd, J=7.8, 1.0 Hz), 1.55 (6H, s). ESI-MS Found: m/z[M+H]+ 216, 218.

  • 2
  • [ 26218-75-7 ]
  • [ 885693-20-9 ]
  • [ 1271809-16-5 ]
YieldReaction ConditionsOperation in experiment
70% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 12h; To a high pressure vessel was added 5-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2- yl)-3,6-dihydro-2H-pyridine-l -carboxylic acid tert-bu yX ester (1.0 g, 3.2 mmol), methyl 6- bromopicolinate (0.77 g, 3.6 mmol), tetrakis(triphenylphosphine)palladium(0) (0.4 g, 0.3 mmol), 1 M of sodium carbonate in water (9.7 mL, 9.7 mmol) and DME (10.1 mL, 97.0 mmol). The reaction was heated for 12 h at 80 °C,then cooled to RT and diluted with water and EtOAc. The organic phase was separated, dried (Na2SC>4), filtered and concentrated in vacuo. The crude material was purified by column chromatography (gradient hexane-EtOAc) to afford the named compound (0.71 g, 70percent yield). .H NMR (CDC13, 300 MHz): delta 7.79 (d, J = 7.55 Hz, 1H), 7.72 (t, J = 7.93 Hz, 1H), 7.44 (d, J = 8.31 Hz, 1H), 4.32-4.41 (m, 1H), 3.90-3.96 (s, 3H), 3.55-3.64 (m, 2H), 2.50 (br. s., 2H), 1.84-1.95 (m, 2H), 1.48 (s, 12H). EIMS (m/z): calcd. for Ci7H2204N2 (M-C4H9, +1H) 263, found 263.
  • 3
  • [ 26218-75-7 ]
  • (1,10-phenanthroline)(trifluoromethyl)copper(I) [ No CAS ]
  • [ 155377-05-2 ]
  • 4
  • [ 26218-75-7 ]
  • 1,10-phenanthroline trifluoroacetic acid cuprous (I) [ No CAS ]
  • [ 155377-05-2 ]
  • 5
  • [ 26218-75-7 ]
  • [(2,2'-bipyridine)2Cu][O2CCF2Cl] [ No CAS ]
  • [ 155377-05-2 ]
  • 7
  • [ 26218-75-7 ]
  • [ 75-16-1 ]
  • [ 638218-78-7 ]
YieldReaction ConditionsOperation in experiment
81% In tetrahydrofuran; at 0 - 20℃;Inert atmosphere; Into a 2000-mL 4-necked round- bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed methyl 6-bromopyridine-2-carboxylate (43.2 g, 199.97 mmol, 1.00 equiv), tetrahydrofuran (700 mL). This was followed by the addition of bromo(methyl)magnesium (150 mL) dropwise with stirring at 0C. The resulting solution was stirred overnight at room temperature. The mixture was then quenched by the addition of 200 mL of water. The resulting solution was extracted with 3x200 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2x200 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 35 g (81%) of 2-(6-bromopyridin-2-yl)propan-2- ol as yellow oil.
  • 8
  • [ 26218-75-7 ]
  • [ 22237-13-4 ]
  • methyl 6-(4-ethoxyphenyl)picolinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; caesium fluoride; In 1,2-dimethoxyethane; at 80℃;Schlenk technique; Inert atmosphere; General procedure: A Schlenk tube was dried under vacuum and charged with 1 0 eq halogenated substrate, 1.1 eq boronic acid, 5 mol% PdCb(dppf), 2.1 eq CsF, and anhydrous DME (~5 mL/100 mg halogenated substrate). The mixture was degassed via three cycles of vacuum/inert gas and was stirred at 80 C (oil-bath) overnight, after which time the reaction mixture was cooled to rt and optionally filtered through a pad of silica get or cotton. Subsequently, the solvent was removed under reduced pressure and final purification via column chromatography yielded the pure product. Reaction control was performed via TLC analysis and/or GC-MS analysis
 

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