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Chemical Structure| 1258283-17-8 Chemical Structure| 1258283-17-8

Structure of 1258283-17-8

Chemical Structure| 1258283-17-8

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Product Details of [ 1258283-17-8 ]

CAS No. :1258283-17-8
Formula : C6H6BrNO3
M.W : 220.02
SMILES Code : O=C(C1=C(Br)N=CO1)OCC
MDL No. :MFCD20260216
InChI Key :ARPHYGHAUCJWCC-UHFFFAOYSA-N
Pubchem ID :57345812

Safety of [ 1258283-17-8 ]

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

Computational Chemistry of [ 1258283-17-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 5
Fraction Csp3 0.33
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 40.29
TPSA ?

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

52.33 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.1
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

1.91
Log Po/w (WLOGP)?

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

1.61
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.

0.36
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

1.65
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.53

Water Solubility

Log S (ESOL):?

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

-2.55
Solubility 0.626 mg/ml ; 0.00285 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.

-2.63
Solubility 0.513 mg/ml ; 0.00233 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

-2.58
Solubility 0.58 mg/ml ; 0.00264 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.

-6.29 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)

2.36

Application In Synthesis of [ 1258283-17-8 ]

* 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 [ 1258283-17-8 ]

[ 1258283-17-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 118994-89-1 ]
  • [ 1258283-17-8 ]
YieldReaction ConditionsOperation in experiment
30% With bromine; lithium hexamethyldisilazane; In tetrahydrofuran; N,N-dimethyl-formamide; at -60℃; for 4h; To a solution of <strong>[118994-89-1]ethyl oxazole-5-carboxylate</strong> (0.28 g, 2.00 mmol) in THF/DMF (2/2 mL) was added Br2 (0.13 mL, 2.6 mmol, 1.3 eq.) and LHMDS (2.6 mL 2.6 mmol, 1.3 eq) to obtain a reaction mixture, which was stirred at -60 C. for 4 hours. The reaction mixture was extracted with EA and water and the combined organic layer was dried with MgSO4. The residue was purified by flash chromatography with EA/Hex (EA/Hex=1:4) to give OS-a.1 as yellow oil (0.1 g, 30%).
4-bromo<strong>[118994-89-1]oxazole-5-carboxylic acid ethyl ester</strong>To a solution of <strong>[118994-89-1]oxazole-5-carboxylic acid ethyl ester</strong> (12.2 g) in a mixture of tetrahydrofuran (70 ml.) and 1 ,3-dimethyl-3,4,5,6-tetrahydro-2(1 H)-pyrimidinone (70 ml.) was added, over 30 minutes at -65 to -78C under nitrogen, a 1.0 M solution of 1 ,1 ,1 ,3,3,3-hexamethyldisilazane lithium salt in tetrahydrofuran (110 ml_). The solution was stirred at -780C for 80 minutes, then bromine (5.8 ml_) was added dropwise over 20 minutes and the resulting mixture was stirred at -780C for a further 45 minutes. The cold solution was added to a mixture of te/t-butylmethyl ether (50O mL) and 10% aqueous sodium thiosulfate solution (500 ml_) at room temperature. The phases were separated and the organic layer was washed with water and brine, then dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a mixture of diethyl ether and pentane (0:1 to 1 :1 by volume), to afford the title compound (2.44 g) as a solid mass.MS: ESI (+ve) (Method E): 220 (M+H)+, Retention time 3.27 min.
With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; bromine; Ethyl 4-bromooxazole-5-carboxylate (2) To a solution of <strong>[118994-89-1]ethyl oxazole-5-carboxylate</strong> (1) (100.0 g, 0.71 mol) in THF (500 mL) and DMPU (500 mL) was added LiHMDS (1.0 M, 921 mL, 921 mmol) dropwise at -78 C. under N2 atmosphere, and the mixture was stirred for 1.5 hours. Then Br2 (54.5 mL, 1.06 mol) was added dropwise at the same temperature and the resulting mixture was stirred for 0.5 hours. TLC showed the starting material disappeared. The resulting solution was poured into a room temperature saturated aqueous NH4Cl (1000 mL), extracted with EtOAc (500 mL*3). The combined organic layers were washed with brine (500 mL*2), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by MPLC to give ethyl 4-bromooxazole-5-carboxylate (25.0 g, purity: 90%, yield: 11%) as yellow oil. 1H NMR (400 MHz, CHCl3-d): delta 7.94 (s, 1H), 4.43 (q, J=7.3 Hz, 2H), 1.42 (t, J=7.2 Hz, 3H)
 

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