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Chemical Structure| 215800-05-8

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Product Details of [ 215800-05-8 ]

CAS No. :215800-05-8
Formula : C9H8BrN
M.W : 210.07
SMILES Code : CC1=C(CC#N)C=CC(Br)=C1
MDL No. :MFCD14582920
InChI Key :JVPNKXZIJKBMDH-UHFFFAOYSA-N
Pubchem ID :18414296

Safety of [ 215800-05-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 215800-05-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 48.63
TPSA ?

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

23.79 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.12
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

2.63
Log Po/w (WLOGP)?

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

2.82
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.

2.82
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

3.27
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.73

Water Solubility

Log S (ESOL):?

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

-3.14
Solubility 0.153 mg/ml ; 0.00073 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.

-2.78
Solubility 0.349 mg/ml ; 0.00166 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

-4.13
Solubility 0.0154 mg/ml ; 0.0000735 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

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.

-5.71 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

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)

1.45

Application In Synthesis of [ 215800-05-8 ]

* 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 [ 215800-05-8 ]

[ 215800-05-8 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 151-50-8 ]
  • [ 156001-49-9 ]
  • [ 215800-05-8 ]
YieldReaction ConditionsOperation in experiment
In water; N,N-dimethyl-formamide; at 80℃; for 72h; Step 3: (4-bromo-2-methylphenvD acetonitrile; KCN (1.4 eq.) was added to a stirred solution of the benzyl bromide in DMF (0.22M) and a small amount of water (1%). The suspension was stirred 72h at 80 C. The reaction was monitored by NMR of small aliquots. The final mixture was cooled down to room temperature, poured in water and extracted with Et2theta. The organic extract was washed with water (2x), brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel, eluting with Hexane/EtOAc (5 then 10%) to give the title compound III.l as a yellow solid.
  • 2
  • [ 143-33-9 ]
  • [ 156001-49-9 ]
  • [ 215800-05-8 ]
YieldReaction ConditionsOperation in experiment
93% In water; N,N-dimethyl-formamide; at 0 - 20℃; Step c intermediate 522-(4-bromo-2-methylphenyl)acetonitrilel-Bromo-4-(bromomethyl)-3-methylbenzene (13.2 g, 50.1 mmol) is dissolved in DMF (65 mL). The reaction mixture is cooled to 0-50C and NaCN (3.66 g, 74.6 mmol) is added follow by water (8 mL). The reaction is stirred overnight at room temperature and water (170 mL) is added followed by NaHCO3 sat. (130 mL) and hexane/Et2O (2:1) (150 mL). The organic phase is separated and the aqueous phase extracted with hexane / Et2O (2:1) (3 x 150 mL). The combined organic phases are washed with water (170 mL), dried over MgSO4, filtered and concentrated under reduced pressure to provide the expected product 2-(4-bromo-2-methylphenyl)acetonitrile (9.76 g, 93 %) as an orange oil. IH NMR (300 MHz, CHLOROFORM-D): delta 7.40-7.32 (2H, m), 7.23 (2H, d, /= 8.2 Hz), 3.61 (2H, s), 2.32 (3H, s).
92.7% In water; N,N-dimethyl-formamide; at 20℃; To a solution of 4-bromo-1-bromomethyl-2-methyl-benzene (3.96 g, 15 mmol) dissolved in DMF (16. mL)( were, a'dd^jspdjum cyanide (0.85 g, '17.25 mmol) and waler (1.8 ml). The reaction was sti'rred for oye'rriigh't at room temperature. To the reaction was added 1 00 ml water; 80 mL saturated NaHCO3, and 100 mL EtOAc. The layers were separated, and the aqueous layer was extracted with 3 x 100 mL EtOAc. The combined organics were washed with 100 mL water, and then dried over Na2SO4. After filtering off the solids, the mother liquor was concentrated to the desired product by rotary evaporation (2.92 g, 92.7% yield). 1H NMR (400 MHz, CDCI3): 6 2.32 (2 H, s), 3.62 (1 H, s), 7.20-7.27 (1 H, m), 7.32-7.41 (1 H, m).
  • 3
  • potassium cyanide [ No CAS ]
  • [ 156001-49-9 ]
  • [ 215800-05-8 ]
YieldReaction ConditionsOperation in experiment
With tetrabutylammomium bromide; In dichloromethane; water; at 0 - 20℃; for 16h; To a solution of 4-bromo- l -(bromomethyl)-2-methylbenzene 133 (3.8) in a mixture of DCM and water was added TBAB and KCN (2.94 g) at 0 C. The mixture was stirred for 16 h at room temperature. DCM was added and the mixture was washed with water and saturated aq NaHCCh. The organic layer was separated, dried over Na2S04, and concentrated under reduced pressure to afford 2-(4-bromo-2-methylphenyl)acetonitrile 134 as a brown solid (2.9 g). The compound was used in the next reaction without further purification. LCMS: m/z 210 (M+l )+.
  • 4
  • [ 773837-37-9 ]
  • [ 156001-49-9 ]
  • [ 215800-05-8 ]
YieldReaction ConditionsOperation in experiment
95% In water; N,N-dimethyl-formamide; at 20℃; for 5h;Inert atmosphere; NaCN (2.78 g, 56.80mmol, 1.5 eq) was added to the solution of <strong>[156001-49-9]4-bromo-1-(bromomethyl)-2-methylbenzene</strong> (10.00 g, 37.80 mmol, 1.0 eq) in DMF and H20 (10:1, 110 mL) under nitrogen atmosphere and thesolution was stirred at ambient temperature for 5 h. After complete consumption of starting material, the reaction mixture was diluted with ice cold water and extracted with diethyl ether. The organic extract was then washed with water, dried over anhydrous sodium sulfate, filtered, and solvent evaporated from the filtrated under reduced pressure to afford 2-(4-bromo-2- methylphenyl)acetonitrile as off white solid (7.5 g, 95%).
  • 5
  • [ 215800-05-8 ]
  • [ 34270-90-1 ]
  • 4-(4-bromo-2-methylphenyl)oxane-4-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% Sodium bis(trimethylsilyl)amide solution in THF (1M, 19.5 mL, 19.5 mmol) was added dropwise to a solution of 2-(4-bromo-2-methylphenyl)acetonitrile (3.75 g, 17.85 mmol) in THF (90 mL) at 0C. After stirring for 0.5 h, the cooling bath was removed and the reaction mixture was stirred at 20C for 0.5 h. l-Iodo-2-(2-iodoethoxy)ethane (2.8 mL, 19.67 mmol) was added dropwise. The reaction mixture was stirred for 0.5 h at 20C. Sodium bis(trimethylsilyl)amide solution in THF (1M, 19.5 mL, 19.5 mmol) was added dropwise. The reaction mixture was stirred for 18 h at 20C, then quenched with saturated aqueous ammonium chloride solution (25 mL) and diluted with water (25 mL). The aqueous layer was extracted with EtOAc (3 x 50 mL). The combined organic extracts were washed with brine (50 mL) and dried over sodium sulfate, then filtered and concentrated in vacuo. The resulting brown oil was separated by flash column chromatography on silica, using a gradient of fc/7-butyl methyl ether in heptane (0-25%), to afford the title compound (2.3 g, 45%) as a yellow solid. 6n (250 MHz, CDCb) 7.47- 7.36 (m, 2H), 7.16 (d, 8.4 Hz, 1H), 4.16-4.06 (m, 2H), 4.06-3.91 (m, 2H), 2.65 (s, 3H), 2.33-2.21 (m, 2H), 2.17-1.99 (m, 2H). HPLC-MS (method 9): [M+water]+ m/z 297 and 299, RT 1.80 minutes.
 

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