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Chemical Structure| 706819-66-1 Chemical Structure| 706819-66-1

Structure of 706819-66-1

Chemical Structure| 706819-66-1

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Product Details of [ 706819-66-1 ]

CAS No. :706819-66-1
Formula : C6H7BrN2O
M.W : 203.04
SMILES Code : CN1C=C(C=N1)C(=O)CBr
MDL No. :MFCD11182388
InChI Key :WFSBGKUQQQMDJU-UHFFFAOYSA-N
Pubchem ID :43144152

Safety of [ 706819-66-1 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314-H290
Precautionary Statements:P501-P260-P234-P264-P280-P390-P303+P361+P353-P301+P330+P331-P363-P304+P340+P310-P305+P351+P338+P310-P406-P405
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 706819-66-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 5
Fraction Csp3 0.33
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 41.55
TPSA ?

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

34.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.36
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

0.71
Log Po/w (WLOGP)?

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

1.0
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.

0.27
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

1.17
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.9

Water Solubility

Log S (ESOL):?

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

-1.78
Solubility 3.34 mg/ml ; 0.0164 mol/l
Class?

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

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.02
Solubility 19.4 mg/ml ; 0.0954 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

-2.01
Solubility 1.99 mg/ml ; 0.00982 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

No
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.

-7.03 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)

1.79

Application In Synthesis of [ 706819-66-1 ]

* 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 [ 706819-66-1 ]

[ 706819-66-1 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 37687-18-6 ]
  • [ 706819-66-1 ]
YieldReaction ConditionsOperation in experiment
89% With pyridinium perbromide hydrobromide; In ethanol; dichloromethane; at 20℃; for 3h; B. Synthesis of 2-bromo-<strong>[37687-18-6]1-(1-methyl-1H-pyrazol-4-yl)ethanone</strong> A solution of <strong>[37687-18-6]1-(1-methyl-1H-pyrazol-4-yl)ethanone</strong> (28.5 g, 230 mmol) in dichloromethane (400 mL) was diluted with absolute ethanol (100 mL) and treated portion-wise with pyridinium tribromide (95%, 77.3 g, 230 mmol). The reaction was stirred at room temperature for 3 hours, during which time it solidified; the mixture was diluted with dichloromethane (300 mL) and water (400 mL), treated with sodium sulfite (5 g) and stirred for 10 minutes. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was washed with water (200 mL), collected by filtration, washed again with water, and dried to afford the product as an off-white solid. Yield: 41.6 g, 205 mmol, 89%. 1H NMR (500 MHz, CDCl3) delta 7.97-7.98 (m, 1H), 7.95 (br s, 1H), 4.17 (s, 2H), 3.95-3.96 (m, 3H).
85% With pyridine hydrobromide perbromide; In ethanol; dichloromethane; at 15℃; for 18h;Inert atmosphere; Large scale; Two identical reactions were carried out in parallel.10159] To a solution of i-(i-methyl-iH-pyrazol-4-yl) ethan-i-one (Preparation 5, 620 g, 5 mol) in DCM (12 L) and ethanol (3 L) was added PyHl3r3 (1.6 kg, 5 mol) at about 15 C. The mixture was stirred at about 15 C. for about 18 hrs. The two reaction mixtures were combined, quenched with water (10 L), separated, and the aqueous phase was extracted with DCM (4xiO L). The combined DCM extracts were dried (Na2SO4) and concentrated to remove about 69 L of solvent. The residue was diluted with petroleum ether (5 L), stirred at about 15 C. for about 30 mm and the mixture was filtered. The precipitate was dried to afford the title compound as a yellow solid (1.73 kg, 85%).?H NMR (400 MHz, CDCl3) delta: 7.97 (s, iH), 7.91 (s, 1H), 4.17 (s, 2H), 3.93 (s, 3H). LCMS mlz=203.i [MH] (798r isotope)
20% With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 24h;Reflux; UV-irradiation; 1-(1-Methyl-1H-pyrazol-4-yl)ethanone (18 g, 145 mmol) and NBS (31 g, 174 mmol) were added to the reaction flask.Add CCl4 (80 mL) to dissolve, and add AIBN (2.4 g, 14.5 mmol) in portions under reflux, and react under 365 nm UV irradiation for 24 h.After the reaction is completed, the system is poured into ice water, extracted with dichloromethane, dried over anhydrous sodium sulfate, and the solvent is removed for column chromatography.(eluent: Petroleum ether/EtOAc (v/v) = 5/1),5.9 g of a yellow oily product were obtained in a yield: 20%.
With hydrogen bromide; bromine; In chloroform; acetic acid; at 20℃; for 1h; 2-Bromo- 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethanoneTo a solution of 1 -(I -methyl- lH-pyrazol-4-yl)ethanone (0.602 g, 4.85 mmol) in chloroform (20 mL) and of 33% HBr in acetic acid (3.92 mg, 0.05 mmol) was added dropwise a chloroform solution containing Br2 (0.262 mL, 5.09 mmol) via an addition funnel. The reaction mixture was stirred at room temperature for 1 h and then concentrated under reduced pressure. The crude solid was triturated in ethyl acetate, filtered, washed and dried in vacuo. The free base was obtained by triturating the product in 5% NaHCtheta3 for 2 h. The solid that formed were collected by filtration, washed with water and isopropyl alcohol and then dried in vacuo. Isolation gave 874 mg of the title compound. LC/MS (ES+)(M+H)+: 204 for C6H7BrN2O.1H NMR (300 MHz, d6-DMSO): 3.88 (s, 3H), 4.56 (s, 2H), 7.99 (s, IH), 8.47 (s, IH).
With bromine; acetic acid;hydrogen bromide; In chloroform; at 20℃; for 1h; Intermediate 282-Bromo- 1 -( 1 -methyl- 1 H-pyrazol-4-vDethanoneIn a 25 mL flask, 1 -(I -methyl- lH-pyrazol-4-yl)ethanone (0.602 g, 4.85 mmol) was dissolved in chloroform (20 mL). The colorless solution was made acidic with the addition of a few drops of HBr in acetic acid (3.92 mg, 0.05 mmol). A chloroform solution containing Br2 (0.262 mL, 5.09 mmol) was added dropwise via an addition funnel. The reaction mixture was stirred at room temperature for 1 h, and then concentrated under reduced pressure. The crude solid was triturated in ethyl acetate, filtered, and dried in vacuo. The free base was obtained by triturating the product in 5% NaHCCb for 2 h. The solid was collected by filtration, washed with water, isopropyl alcohol and then dried in vacuo. Isolation gave 874 mg of the title compound.LC/MS (ES+)[(M+H)+]: 204 for C6H7BrN2O.1H NMR (300 MHz, d6-DMSO): 3.88 (s, 3H), 4.56 (s, 2H), 7.99 (s, IH), 8.47 (s, IH).
2 g With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; at 80℃; for 14h; Method 31 Synthesis of 2-bromo-1-(6-methyl-3-pyridyl)ethanone (Intermediate 45) To a solution of R-12 (10 g, 79.3 mmol) in MeCN (200 mL) at 0 C. is added N,O-dimethylhydroxylaminehydrochloride (8.5 g, 87.2 mmol), EDCI (18.2 g, 95.2 mmol), 1-hydroxybenzotriazole (3.2 g, 23.8 mmol) followed by triethylamine (20.5 mL, 158 mmol) and stirred at room temperature 15 h. The reaction mixture is partitioned between water and EtOAc. The collected organics are dried with anhydrous Na2SO4, filtered, and concentrated in vacuo to give I-43 (12 g) m/z 170.0 [M+H].

 

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