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Chemical Structure| 81971-39-3 Chemical Structure| 81971-39-3
Chemical Structure| 81971-39-3

5-Bromo-1-methylpyridin-2(1H)-one

CAS No.: 81971-39-3

4.5 *For Research Use Only !

Cat. No.: A102696 Purity: 97%

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Product Details of [ 81971-39-3 ]

CAS No. :81971-39-3
Formula : C6H6BrNO
M.W : 188.02
SMILES Code : CN1C=C(Br)C=CC1=O
MDL No. :MFCD09972188
InChI Key :HHVFVHIUOMMWRN-UHFFFAOYSA-N
Pubchem ID :13024027

Safety of [ 81971-39-3 ]

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

Calculated chemistry of [ 81971-39-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 39.66
TPSA ?

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

22.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.91
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

0.8
Log Po/w (WLOGP)?

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

1.15
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.

1.38
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

1.6
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.37

Water Solubility

Log S (ESOL):?

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

-2.0
Solubility 1.87 mg/ml ; 0.00993 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.

-0.84
Solubility 27.0 mg/ml ; 0.143 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very 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

-2.35
Solubility 0.844 mg/ml ; 0.00449 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.

-6.88 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

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)

1.52

Application In Synthesis of [ 81971-39-3 ]

* 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 [ 81971-39-3 ]

[ 81971-39-3 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 81971-39-3 ]
  • [ 73183-34-3 ]
  • [ 1002309-52-5 ]
YieldReaction ConditionsOperation in experiment
23.6% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 2h;Microwave irradiation; A solution of 5-bromo-1-methylpyridin-2-one (200.0 mg, 1.06 mmol), bis(pinacolato)diboron (410.0 mg, 1.61 mmol), potassium acetate (270 mg, 2.67 mmol), Pd (dppf)Cl2 (80 mg, 0.11 mmol) in dioxane (5 mL) was heated at 100° C. for 2 h under microwave. The mixture was filtered, washed with water and extracted with ethyl acetate (20 mL*3). The combined organics were dried over Na2SO4, filtered and concentrated to give the crude title compound (59.0 mg, 23.6percent). LCMS (M+H)+ 236.
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In dimethyl sulfoxide; at 80℃; for 0.5h; To a solution of 5-bromo-1-methylpyridin-2(1H)-one (800 mg) in DMSO (21 ml) was added bis(pinacolato)diboron (1620 mg), potassium acetate (1253 mg) and 1,1'-bis(diphenyl-phosphino)ferrocene-palladium(II)dichloride dichloromethane adduct (213 mg). The reaction mixture was stirred at 80°C for 30 min. The reaction was diluted with water (20 ml) and extracted with EtOAc (3 x 30 ml). The organic layer was dried with Na2SO4 and solvents were reduced under reduced pressure. The crude product was purified by flash chromatography.
With sodium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 120 - 130℃; for 8.5h; 5-Bromo-l-methylpyridin-2 (IH) -one (0.100 g, 0.532 mmol) was suspended in dioxane (2 mL) then added 4,4,5,5- tetramethyl-2- (4,4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) - 1, 3, 2-dioxaborolane (0.203 g, 0.798 mmol), PdC12 (dppf) - CH2C12Adduct (0.0217 g, 0.0266 mmol) and sodium acetate (0.109 g, 1.33 mmol) . The reaction mixture was heated at 120 0C for 5.5 hours then at 130 0C for 3 hours. The reaction mixture was <n="119"/>filtered through a pad of Celite, washing with MeOH. The filtrate was concentrated under vacuum. The remaining black residue was then dissolved in dichloromethane and filtered through another pad of Celite, washing well with dichloromethane. The filtrate was concentrated under vacuum and the remaining black residue was further dried under high vacuum to afford l-methyl-5- (4,4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2- yl)pyridin-2 (IH) -one as a black solid. MS (ESI pos. ion) m/z: 236.1 (MH+).
With potassium acetate;palladium bis[bis(diphenylphosphino)ferrocene] dichloride; In dichloromethane; N,N-dimethyl-formamide; at 80℃; for 10h; Example 9N-(3-fluoro-4-(l-methyl-6-oxo-l,6-dihvdropyridin-3-yl)benzyl)-4-(pyrazin-2-yl)benzamideCompound 21[0174] Step 1: A mixture of 5-bromo-l-methylpyridin-2(lH)-one 21-1 (350 mg, 1.87 mmol), (4,4',4',5,5,5',5'-heptamethyl-[2,2'-bi(l,3,2-dioxaborolan)]-4-yl)methylium 21-2 (617 mg, 2.43 mmol), potassium acetate (550 mg, 5.61 mmol) and Pd(dppf)2Cl2 dichloromethane complex (82 mg, 0.1 mmol) in DMF (10 mL) was stirred at 80 °C for 10 hours. After cooling to room temperature, the mixture was filtered through celite, concentrated by evaporation under reduced pressure and then redistributed between ethyl acetate and water. The organic phase was dried over Na2S04 and concentrated by evaporation under reduced pressure. The resulting residue was subjected to silica gel column chromatography with 1: 1 ethyl acetate/hexanes as eluent to give l-methyl-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyridin-2(lH)-one 21-3.
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 115℃;Inert atmosphere; Reflux; Preparation of Compound 2222a 22b To a dry flask was added 5-bromo-l-methylpyridin-2(lH)-one 22a (1.0 g, 5.32 mmol), potassium acetate (1.57 g, 15.96 mmol, 3.0 equiv), bis(pinacolato)diboron (1.49 g, 5.85 mmol, LI equiv) and 1,4-dioxane (25 mL). Nitrogen was bubbled through the solution for 10 minutes, at which time dichloro[l,l'-bis(diphenylphosphino)ferrocene] palladium (II) dichloromethane adduct (217 mg 0.27 mmol, 0.05 equiv) was added. The reaction mixture was refluxed at 115 °C overnight under nitrogen. After cooling to room temperature, EtOAc (30 mL) was added and the resulting slurry was sonicated and filtered. Additional EtOAc (20 mL) was used to wash the solids. The combined organic extracts was concentrated and purified by flash chromatography (90percent EtOAc/ hexanes) to yield 22b (520 mg).Compound 22 was prepared analogous to the preparation of 2 but using compound 22b.
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 110℃; for 0.5h; General procedure: A mixture of 3-bromo-1-methylpyridin-2(1H)-one (Step 1 of Example 25, 770 mg, 4.1 mmol),bis(pinacolato)diboron (1248 mg, 4.91 mmol), PdCI2(dppf)CH2CI2 complex (401 mg, 0.491mmol) and potassium acetate (1206 mg, 12.29 mmol) in dioxane (16 mL) was stirred for 2 h at 110 00. The reaction mixture was diluted with toluene, sonicated for 30 mm at 40°C and filtered (the filter cake was rinsed with hot toluene). The filtrate was concentrated to afford the title compound (1.7 g, purity 40percent) as a brown oil. The title compound was prepared using an analogous procedure to that described in Step 2 of Example 25 using 5-bromo-1-methylpyridin-2(1H)-one (ABCR, 1.05 g, 5.58 mmol) and stirringthe reaction mixture for 30 mm at 110°C. The title compound (2.75 g, purity 30percent) was used without purification. Rt: 0.83 mm (LC-MS 1); MS m/z: 236.2 [M+H] (boronic acid) (LC-MS 1).
160 mg With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In ethylene glycol; at 80℃; for 3h; To a stirred suspension of 5-bromo-l-methylpyridin-2(lH)-one (470 mg, 2.49 mmol), potassium acetate (736 mg, 7.49 mmol) and bis(pinacolato)diboron (952 mg, 3.74 mmol) in degassed polyethylene glycol-400 (15 mL) was added [1, 1 '- bis(diphenylphosphino)ferrocene]dichloropalladium (II) (204 mg, 0.24 mmol) at RT. The resultant suspension was stirred for 3 h at 80 °C. The reaction mixture was cooled to RT, diluted with ethyl acetate (100 mL) and washed with water (100 mL) followed by brine (100 mL). The organic layer was concentrated and the residue obtained purified by flash column chromatography to afford 160 mg of the titled product; 1H NMR (300 MHz, CDC13) delta 1.30 (s, 12H), 3.54 (s, 3H), 6.53 (d, J = 9.3 Hz, 1H), 7.60 (d, J = 9.0 Hz, 1H), 7.75 (s, 1H); APCI- MS (m/z) 236 (M+H)+.

 

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