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Chemical Structure| 718608-10-7 Chemical Structure| 718608-10-7

Structure of 718608-10-7

Chemical Structure| 718608-10-7

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Product Details of [ 718608-10-7 ]

CAS No. :718608-10-7
Formula : C7H9Br2N
M.W : 266.96
SMILES Code : CC1=NC=C(CBr)C=C1.[H]Br
MDL No. :MFCD12031798
InChI Key :HEDJZTHUYQRPRW-UHFFFAOYSA-N
Pubchem ID :22145605

Safety of [ 718608-10-7 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H314
Precautionary Statements:P260-P264-P270-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P405-P501
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 718608-10-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.29
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 52.08
TPSA ?

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

12.89 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

2.78
Log Po/w (WLOGP)?

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

3.09
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.

2.1
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

2.81
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.16

Water Solubility

Log S (ESOL):?

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

-3.62
Solubility 0.0634 mg/ml ; 0.000237 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.

-2.71
Solubility 0.525 mg/ml ; 0.00196 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

-3.67
Solubility 0.0571 mg/ml ; 0.000214 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.

-5.95 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

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<0.0
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)

1.91

Application In Synthesis of [ 718608-10-7 ]

* 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 [ 718608-10-7 ]

[ 718608-10-7 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 34107-46-5 ]
  • [ 718608-10-7 ]
YieldReaction ConditionsOperation in experiment
With dibromo sulfoxide; In dichloromethane; at 20℃; for 3h; A solution of (6-METHYLPYRIDIN-3-YL) METHANOL (J. Med. Chem. 43; 18 ; 2000; 3386) (492mg, 4MMOL) and thionyl bromide (4.16g, 20MMOL) in dichloromethane (20ML) was stirred at room temperature for 3 hours. The reaction was concentrated under reduced pressure and the residue azeotroped with DICHLOROMETHANE. The residual red oil was triturated well with ether to afford the title compound as an orange powder, 1.39g ;'H NMR (DMSOd6, 400MHZ) 8 : 2.64 (s, 3H), 4.81 (s, 2H), 7.81 (d, 1 H), 8.42 (d, 1 H), 8.84 (s, 1 H).
  • 2
  • [ 718608-10-7 ]
  • [ 718608-06-1 ]
  • [ 718608-12-9 ]
YieldReaction ConditionsOperation in experiment
Sodium hydride (800mg, 60% dispersion in mineral oil, 20MMOL) and imidazole (54mg, 0. 8MMOL) were added portionwise to a cooled (-15C) solution of the acid from preparation 37 (960mg, 4MMOL) in tetrahydrofuran (40ML) and the solution stirred for 1 hour. A suspension of the bromide from preparation 40 (1.28g, 4. 8MMOL) and N-methyl morpholine (535mg, 5. 3MMOL) in TETRAHYDROFURAN (10M .) was added so as to maintain the temperature BELOW-1 5C, and the reaction then stirred for a further 2 hours. The reaction was allowed to warm to room temperature and stirred for a further 18 hours. The mixture was then basified to pH 11, washed with ethyl acetate, carefully acidifed to pH 5 and extracted with ethyl acetate. These combined organic solutions were washed with brine, dried (MGS04) and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using DICHLOROMETHANE : methanol (94: 6) as eluant, and the product triturated with ether to afford the title compound, 177mg ;'H NMR (CDC13, 400MHZ) 8 : 1.42 (s, 9H), 2.62-2. 80 (m, 5H), 3.64 (m, 2H), 4.18 (m, 1 H), 4.60 (s, 2H), 5.50 (d, 1 H), 7.40 (d, 1 H), 7.83 (d, 1 H), 8.62 (s, 1 H) ; LRMS: M/Z (ES-) 323 [M-H]-.
  • 3
  • [ 718608-10-7 ]
  • 8-chloro-3-((1S,2S)-2-hydroxycyclohexyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazolin-4(3H)-one [ No CAS ]
  • 8-chloro-3-((1S,2S)-2-hydroxycyclohexyl)-6-((6-methylpyridin-3-yl)methyl)quinazolin-4(3H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In tetrahydrofuran; at 60℃; for 2h;Inert atmosphere; A mixture of 8-chloro-3-((1S,2S)-2-hydroxycyclohexyl)-6-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)quinazolin-4(3H)-one (130 mg, 0.321 mmol), cesium carbonate (314 mg, 0.964 mmol) and <strong>[718608-10-7]5-(bromomethyl)-2-methylpyridine hydrobromide</strong> (103 mg, 0.385 mmol) in THF (5.0 ml) was sparged under nitrogen for 5 minutes. The mixture was treated with [1,1?- bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (26.2 mg, 0.032 mmol), sparged under nitrogen (3 minutes) and then heated at 60 C for 2 hours. The mixture was cooled to room temperature, diluted with ethyl acetate (25 mL) and water (25 mL), and extracted with ethyl acetate (3 x 25 mL). The combined organic extracts were washed with brine, dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by preparative reverse phase HPLC (90:10 to 0:100; water containing 0.1% formic acid : acetonitrile containing 0.1% formic acid) to yield the title compound. 1H NMR (400MHz, CD3OD): delta 8.35 (d, J = 2.0 Hz, 2H), 8.02 (d, J = 1.6 Hz, 1H), 7.80 (d, J = 2.0 Hz, 1H), 7.62 (d, J = 8.0, 2.0 Hz, 1H), 7.27 (d, J = 8.0 Hz, 1H), 4.51- 4.49 (m, 1H), 4.13 (s, 2H), 4.07- 4.02 (m, 1H), 2.51 (s, 3H), 2.20- 2.10 (m, 1H), 1.97- 1.84 (m, 4H), 1.48- 1.46 (m, 3H) ppm. LRMS C21H23ClN3O2: calc?d 384.1, obs 384.2 (M+H) +.
  • 4
  • [ 718608-10-7 ]
  • 3-(2-hydroxycyclohexyl)-6-(2-hydroxyphenyl)pyrimidin-4(3H)-one [ No CAS ]
  • 3-(2-hydroxycyclohexyl)-6-(2-((6-methylpyridin-3-yl)methoxy)-phenyl)pyrimidin-4(3H)-one [ No CAS ]
  • 5
  • [ 718608-10-7 ]
  • [ 100643-71-8 ]
  • 8-chloro-11-<1-<(6-methyl-3-pyridyl)methyl>-4-piperidylidene>-6,11-dihydro-5H-benzo<5,6>cyclohepta<1,2-b>pyridine [ No CAS ]
  • 6
  • [ 718608-10-7 ]
  • (R)-5'-chloro-3-((S)-1-(4-chlorophenyl)ethyl)-4,6-dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3'-indoline]-2',5(3H)-dione [ No CAS ]
  • (R)-5'-chloro-3-((S)-1-(4-chlorophenyl)ethyl)-1'-((6-methylpyridin-3-yl)methyl)-4,6-dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3'-indoline]-2',5(3H)-dione [ No CAS ]
 

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