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Chemical Structure| 38940-62-4 Chemical Structure| 38940-62-4

Structure of 3-Acetyl-5-bromopyridine
CAS No.: 38940-62-4

Chemical Structure| 38940-62-4

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Synonyms: 1-(5-Bromopyridin-3-yl)ethanone

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Product Details of [ 38940-62-4 ]

CAS No. :38940-62-4
Formula : C7H6BrNO
M.W : 200.03
SMILES Code : C(C)(=O)C1=CC(=CN=C1)Br
Synonyms :
1-(5-Bromopyridin-3-yl)ethanone
MDL No. :MFCD03086033
InChI Key :LDBPZEQZCOUYFT-UHFFFAOYSA-N
Pubchem ID :820423

Safety of [ 38940-62-4 ]

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

Computational Chemistry of [ 38940-62-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 42.13
TPSA ?

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

29.96 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.64
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

1.23
Log Po/w (WLOGP)?

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

2.05
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.

0.89
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

2.33
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.63

Water Solubility

Log S (ESOL):?

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

-2.23
Solubility 1.17 mg/ml ; 0.00585 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.

-1.46
Solubility 6.99 mg/ml ; 0.0349 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

-3.22
Solubility 0.121 mg/ml ; 0.000605 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.

-6.65 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)

1.48

Application In Synthesis of [ 38940-62-4 ]

* 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 [ 38940-62-4 ]

[ 38940-62-4 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 38940-62-4 ]
  • [ 1520-70-3 ]
  • [ 75-16-1 ]
  • [ 1255871-17-0 ]
YieldReaction ConditionsOperation in experiment
A mixture of 1~(5-bromo-pyridin-3-yl)-ethanone (200 mg. 1.000 mmol), ethanesuifonamide (136 mg, 1.250 mmol) and titanium(IV) isopropoxide (586 mul_, 2.0 mmol) in toluene (20 ml) was heated to reflux for 8 h. After concentration, the residue was dissolved in THF (5 ml). A solution of methylmagnesium bromide (1000 mul, 3.00 mmol) was added dropwise at - 50 0C. The resulting mixture was slowly warmed up to room temperature over a course of 2 h. The mixture was stirred at this temperature overnight and quenched with NH4CI solution. After filtration, wash with CH2CI? and concentration, the residue was purified by flash column (Ethyl acetate / heptane, v/v, 10percent to 50percent) and yielded a yellow oil (35 mg). ESI-MS mlz: 309.1 [M+1]f. Retention time "1.22 mialpha 'H NMR (400 MHz, CDCI3): delta 1.43 (t, J * 7.4 Hz, 3H), 1.84 (s. 6H), 2.98 (q, J s 7.4 Hz, 2H)1 5.07 (brs, 1H), 8.04 (s. 1H). 8.66 (s, 1H), 8.77 (s. 1H).
  • 2
  • [ 38940-62-4 ]
  • [ 1520-70-3 ]
  • [ 1427587-76-5 ]
YieldReaction ConditionsOperation in experiment
With titanium(IV) isopropylate; In toluene; at 110℃; Intermediate A-49 N-(2-(5-Bromopyridin-3-yl)propan-2-yl)<strong>[1520-70-3]ethanesulfonamide</strong>A flask was charged with l-(5-bromopyridin-3-yl)ethanone (0.5 g, 2.5 mmol), <strong>[1520-70-3]ethanesulfonamide</strong> (0.341 g, 3.12 mmol) and toluene (25 mL), then titanium tetra- isopropoxide (1.42 g, 5 mmol) was added dropwise. The reaction mixture was heated to 110 °C over night and then concentrated in vacuo to give the imine intermediate (0.73 g) as a light brown oil. A part of this the imine intermediate (0.4 g) was dissolved in THF (10 mL) and the mixture was cooled down to -78 °C. A 3 M solution of methylmagnesium bromide in ether (1.14 mL, 3.43 mmol) was added dropwise at this temperature and the resulting mixture was stirred at -70 °C for 3 h. It was then allowed to warm up to 0 °C before being quenched with a saturated NH4C1 solution (10 mL). The resulting suspension was filtered and the filtrate was extracted with DCM (2 x 30 mL). Combined organics were dried over Na2S04, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 5percent MeOH-DCM gradient to give the title compound (0.1 g, 17 percent) as a yellow oil which was used with no further purification. MS: 307.1 and 309.1 (M+H+).
  • 3
  • [ 38940-62-4 ]
  • [ 1108724-32-8 ]
YieldReaction ConditionsOperation in experiment
36% With (bis-(2-methoxyethyl)amino)sulfur trufluoride; In dichloromethane; at 60.0℃;Sealed tube; Heat the mixture of l-(5-bromopyridin-3-yl)ethanone (500 mg, 2.5 mmol), bis-(2-methoxyethyl)aminosulfur trifluoride (BAST, 2.2 g, 10 mmol) in dichloromethane (8 mL) in a sealed tube at 60C overnight. TLC (PE:EtOAc=l :l) shows the reaction is complete. Concentrate the mixture, purify the residue by flash chromatography (silica gel, PE:EtOAc=l :1) to afford the title compound (200 mg, 36%). MS: (M+1): 222/224.
36% With (bis-(2-methoxyethyl)amino)sulfur trufluoride; In dichloromethane; at 60.0℃;Sealed tube; Heat the mixture of 1-(5-bromopyridin-3-yl)ethanone (500 mg, 2.5 mmol), bis-(2-methoxyethyl)aminosulfur trifluoride (BAST, 2.2 g, 10 mmol) in dichloromethane (8 mL) in a sealed tube at 60 C. overnight. TLC (PE:EtOAc=1:1) shows the reaction is complete. Concentrate the mixture, purify the residue by flash chromatography (silica gel, PE:EtOAc=1:1) to afford the title compound (200 mg, 36%). MS: (M+1): 222/224.
With diethylamino-sulfur trifluoride; In dichloromethane; at 50.0℃; for 18.0h; Step 1. 3-Bromo-5-(l,l-difluoroethyl)pyridine To a stirred solution of l-(5-bromopyridin-3-yl)ethanone (2.4 g, 12 mmol) in 24 mL of CH2CI2 was added DAST (15.5 mL, 96 mmol) dropwise over a period of 10 min. The mixture was heated to 50 C for 18 h. The mixture was cooled to RT and carefully poured into ice-cold 2N NaOH. The layers were separated and the aqueous phase was extracted with CH2CI2. The organic phases were combined, dried over a2S04, and the solvent was removed in vacuo. The crude product was chromatographed on an 80g S1O2 column using 0-30% EtOAc:hexane over 30 min at 60 mL/min. Fractions containing product were combined and the solvents were removed in vacuo to give the title compound. LCMS m/z (M+H)+ = 223.9.
 

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Technical Information

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