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Structure of 1215205-50-7

Chemical Structure| 1215205-50-7

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Product Details of [ 1215205-50-7 ]

CAS No. :1215205-50-7
Formula : C12H13BrO2
M.W : 269.13
SMILES Code : O=C(C1(C2=CC=C(Br)C=C2)CC1)OCC
MDL No. :MFCD15143548
InChI Key :KCCISTCYYRKGFF-UHFFFAOYSA-N
Pubchem ID :53216840

Safety of [ 1215205-50-7 ]

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

Computational Chemistry of [ 1215205-50-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 6
Fraction Csp3 0.42
Num. rotatable bonds 4
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 62.2
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.07
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

3.11
Log Po/w (WLOGP)?

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

2.98
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.

3.14
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

3.75
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.21

Water Solubility

Log S (ESOL):?

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

-3.5
Solubility 0.0851 mg/ml ; 0.000316 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.

-3.33
Solubility 0.126 mg/ml ; 0.000467 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

-4.55
Solubility 0.00759 mg/ml ; 0.0000282 mol/l
Class?

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

Moderately 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

Yes
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

Yes
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.

-5.73 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<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)

1.92

Application In Synthesis of [ 1215205-50-7 ]

* 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.

  • Upstream synthesis route of [ 1215205-50-7 ]

[ 1215205-50-7 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 345965-52-8 ]
  • [ 1215205-50-7 ]
YieldReaction ConditionsOperation in experiment
80% With thionyl chloride In methanol at 0 - 70℃; To a 50 mL round-bottom flask was added l-(4-bromophenyl)cyclopropane-1- carboxylic acid 149a (2 g, 8.30 mmol, 1.00 equiv.) and methanol (20 mL). Thionyl chloride(2.96 g, 24.88 mmol, 3.00 equiv.) was added drop·wise with stirring at 0°C. The resultingmixture was stined at 70 °C ovemight. After cooling to room temperature, the reaction wasquenched by the addition of water/ice. The aqueous mixture was extracted with ethyl acetate5 (50 mL x 2). The combined organic extracts were vvashed with brine (50 rnL x 2, dried overanhydrous sodium sulfate, and concentrated under vacuum. The crude product was purifiedby Flash-Prep-HPLC eluting with EA/PE (from 0percent to 10percent '.vithin 20 rnin) to give methyl1-(4-bromophenyl)cyclopropa.ne-l-carboxyate 149b (l.7g, 80percent;) as colorless oil
References: [1] Patent: WO2018/39386, 2018, A1, . Location in patent: Page/Page column 295; 296.
  • 2
  • [ 14062-25-0 ]
  • [ 1215205-50-7 ]
YieldReaction ConditionsOperation in experiment
85% With 1,8-diazabicyclo[5.4.0]undec-7-ene In dimethyl sulfoxide at 21℃; for 12 h; General procedure: To a 5 mL Schlenk tube were added aryl / heteroaryl acetates 3 (1.0 mmol, 1.0 equiv.), vinyl diphenylsulfonium triflate (434.4 mg, 1.2 mmol, 1.2 equiv.) and DMSO (5 mL). The mixture was stirred at room temperature for 2 min and to the mixture was added DBU (456 mg, 3 mmol, 3.0 equiv.). The mixture was stirred for 12 hours at room temperature till the reaction was complete. To the resulting mixture was added saturated ammonium chloride solution (25 mL), and the mixture was then extracted with EtOAc (3 x 150 mL). The combined organic layers were washed with H2O (2 x 30 mL), dried with anhydrous sodium sulfate. After concentration, product 4 was purified using column chromatography on silica gel using an appropriate eluent.
References: [1] Tetrahedron Letters, 2018, vol. 59, # 14, p. 1443 - 1445.
  • 3
  • [ 14062-25-0 ]
  • [ 106-93-4 ]
  • [ 1215205-50-7 ]
YieldReaction ConditionsOperation in experiment
26% With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 20℃; Example 14A
Ethyl 1-(4-bromophenyl)cyclopropanecarboxylate
1.45 g (36.2 mmol) of sodium hydride in mineral oil (60percent pure) were initially charged in 100 ml of DMF. A mixture of 4.0 g (16.5 mmol) of ethyl (4-bromophenyl)acetate and 6.5 g (34.6 mmol) of 1,2-dibromoethane was dissolved in 50 ml of THF and slowly added dropwise.
The mixture was stirred at RT overnight.
The reaction mixture was diluted with ethyl acetate and washed with water and saturated sodium chloride solution.
The organic phase was separated off, dried over magnesium sulphate and filtered, and the filtrate was concentrated.
The residue was purified by preparative HPLC [Reprosil C18, 10 μm, 250 mm*40 mm (30percent methanol/70percent water to 100percent methanol) over a run time of 25 min].
After HPLC control, the product-containing fractions were combined and concentrated.
This gave 1.15 g (26percent of theory) of a liquid.
GC-MS [Method 5]: Rt=5.45 min; MS(ESIpos): m/z=268/270 (M+)
1H-NMR (400 MHz, DMSO-d6): δ [ppm]=1.09 (t, 3H), 1.16-1.20 (m, 2H), 1.46-1.50 (m, 2H), 4.02 (q, 2H), 7.26-7.31 (m, 2H), 7.47-7.51 (m, 2H)
References: [1] Patent: US2016/318866, 2016, A1, . Location in patent: Paragraph 0642; 0643; 06444; 0645.
  • 4
  • [ 345965-52-8 ]
  • [ 64-17-5 ]
  • [ 1215205-50-7 ]
References: [1] Organic Process Research and Development, 2017, vol. 21, # 11, p. 1859 - 1863.
[2] Patent: WO2010/141761, 2010, A2, . Location in patent: Page/Page column 47.
[3] Patent: US2011/82164, 2011, A1, . Location in patent: Page/Page column 24.
[4] Patent: US2011/82181, 2011, A1, . Location in patent: Page/Page column 16.
[5] Patent: WO2012/78593, 2012, A2, . Location in patent: Page/Page column 124.
[6] Patent: WO2012/78805, 2012, A1, . Location in patent: Page/Page column 92.
[7] Patent: US2012/258987, 2012, A1, . Location in patent: Page/Page column 42.
  • 5
  • [ 16532-79-9 ]
  • [ 1215205-50-7 ]
References: [1] Patent: US2011/82164, 2011, A1, .
[2] Patent: WO2012/78593, 2012, A2, .
[3] Patent: US2011/82181, 2011, A1, .
[4] Patent: WO2012/78805, 2012, A1, .
[5] Patent: US2012/258987, 2012, A1, .
  • 6
  • [ 124276-67-1 ]
  • [ 1215205-50-7 ]
References: [1] Patent: US2011/82164, 2011, A1, .
[2] Patent: WO2012/78593, 2012, A2, .
[3] Patent: US2011/82181, 2011, A1, .
[4] Patent: WO2012/78805, 2012, A1, .
[5] Patent: US2012/258987, 2012, A1, .
 

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