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Product Details of [ 136630-36-9 ]

CAS No. :136630-36-9
Formula : C12H10Br2N2
M.W : 342.03
SMILES Code : NC1=CC(Br)=CC=C1C2=CC=C(Br)C=C2N
MDL No. :MFCD14582981
InChI Key :KZDMFBDNQPKWNM-UHFFFAOYSA-N
Pubchem ID :11221538

Safety of [ 136630-36-9 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H315-H318-H335-H410
Precautionary Statements:P261-P273-P280-P305+P351+P338
Class:9
UN#:3077
Packing Group:

Computational Chemistry of [ 136630-36-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 0.0
Num. H-bond donors 2.0
Molar Refractivity 76.09
TPSA ?

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

52.04 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.46
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

3.57
Log Po/w (WLOGP)?

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

4.06
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.

3.74
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

3.38
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.44

Water Solubility

Log S (ESOL):?

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

-4.7
Solubility 0.00685 mg/ml ; 0.00002 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-4.35
Solubility 0.0153 mg/ml ; 0.0000448 mol/l
Class?

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

Moderately 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

-5.87
Solubility 0.000466 mg/ml ; 0.00000136 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

Yes
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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.85 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)

1.83

Application In Synthesis of [ 136630-36-9 ]

* 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 [ 136630-36-9 ]

[ 136630-36-9 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 136630-36-9 ]
  • [ 852138-89-7 ]
YieldReaction ConditionsOperation in experiment
29% A 17% (w/w) HCl aqueous solution (85mL) at 0C was added to the compound containing (Beta-3) (8 ·5g, 25mmol) of Round-bottomed flask, and to this was added NaNO2 (NaNO2 solution [NaNO24.3g (62mmol) + water (15mL)] was added . The mixture was stirred for 30 minutes, and this was added an aqueous solution of KI [KI 41.5g (250_mmol) + water (15mL) ]. the mixture was stirred at room temperature for 1 hour, at 60 C and stirred for 3 hours. K0H with a saturated solution and extracted with ethyl acetate and washed with saturated Na2SO3 (V Dr Di, the residue was purified by column chromatography to give compound B-4 (4g, 29%).
29% At a temperature of about 0 C., 85 mL of a 17% (w/w) HCl aqueous solution and a NaNO2 aqueous solution including 4.3 g (62 mmol) of NaNO2 and 15 mL of water were added to a round-bottom flask containing 8.5 g (25 mmol) of Intermediate 4-2. The resulting mixture was stirred for about 30 minutes, and a KI aqueous solution including 41.5 g (250 mmol) of KI and 15 mL of water was added thereto, followed by stirring for about 1 hour at room temperature and then stirring at a temperature of about 60 C. for about 3 hours. A saturated KOH solvent was used to neutralize the resulting mixture. An organic layer was extracted therefrom using ethyl acetate, washed with saturated Na2SO3, and purified through silica gel chromatography, thereby producing 4 g (yield: 29%) of Intermediate 4-3.
29% To a round bottom flask containing 8.5 g (25 mmol) of the compound B-3 at 0 C was added 85 mL of 17% (w/w) aqueous HCl solution and an aqueous solution of NaNO2 [4.3 g (62 mmol) of NaNO2 + 15 mL of water] was added. Stirred for 30 minutes and KI aqueous solution [KI 41.5 g (250 mmol) + water 15 mL] was added. Stirred at room temperature for 1 hour and stirred at 60 C for 3 hours. The reaction mixture was neutralized with saturated KOH solvent, extracted with ethyl acetate, washed with saturated Na2SO3 and then purified by silica column to obtain 4 g (29%) of compound B-4.
29.1% 87.7 g (0.256 mol) of 4,4'-dibromo-2,2'-diaminobiphenyl,380 mL of 12 M HCl, and 380 mL of water.The temperature of the reactor was lowered to 0 C.Sodium nitrite (44.2 g, 0.641 mol) was dissolved in 220 mL of water, slowly added dropwise to the reactor,When the addition was complete, the mixture was stirred at the same temperature for 1 hour for 1 hour.Potassium iodide was dissolved in 850 mL of water and slowly added dropwise. When the dropwise addition was completed, the solution was stirred at room temperature for 1 hour.The temperature of the reactor was raised to 60 DEG C and stirred for 3 hours.When the reaction was complete, the mixture was cooled to room temperature and extracted with Ethylacetate to separate the organic layer.The separated organic layer was dried over anhydrous, dried and then subjected to column chromatography using hexane as a developing solvent to obtain 42.1 g (yield: 29.1%) of 4,4'-dibromo-2,2'-diiodobiphenyl.
29.1% 87.7 g (0.256 mol) of 4,4'-Dibromo-2,2'-diaminobiphenyl, 380 mL of 12 M HCl, and 380 mL of water were added thereto. The temperature of the reactor was lowered to 0 C.Sodiumnitrite 44.2 g (0.641 mol) was dissolved in 220 mL of water and slowly added dropwise to the reactor, and when the dropwise addition was completed, the mixture was stirred for 1 hour at the same temperature for 1 hour.Potassium iodide was dissolved in 850 mL of water and slowly added dropwise, and when the addition was completed, the mixture was stirred at room temperature for 1 hour.And the temperature of the reactor was heated up to 60 degreeC and stirred for 3 hours. After the reaction was completed, the reaction mixture was cooled to room temperature and extracted with ethylacetate to separate the organic layer. The organic layer was dried over anhydrous and dried, and then separated by column chromatography using hexane as a developing solvent, to obtain 42.1g (29.1%) of 4,4'-dibromo-2,2'-diodiobiphenyl.
29.1% 87.7 g (0.256 mol) of 4,4'-Dibromo-2,2'-diaminobiphenyl, 380 mL of 12 M HCl, and 380 mL of water were added thereto. The temperature of the reactor was lowered to 0 C.Dissolve 44.2 g (0.641 mol) of sodium nitrite in 220 mL of water and slowly add it to the reactor,When the dropwise addition was completed, the mixture was stirred for 1 hour at the same temperature.Potassium iodide was dissolved in 850 mL of water and slowly added dropwise, and when the addition was completed, the mixture was stirred at room temperature for 1 hour. And the temperature of the reactor was heated up to 60 degreeC and stirred for 3 hours.After the reaction was completed, the reaction mixture was cooled to room temperature and extracted with Ethylacetate to separate the organic layer.The organic layer was dried over anhydrous and dried, and then separated by column chromatography using hexane as a developing solvent, to obtain 42.1g (29.1%) of 4,4'-dibromo-2,2'-diodiobiphenyl.
29% [Intermediate 5-b] (87.7 g, 0.256 mol) synthesized in [Scheme 5-2] was added to 380 mL of 12 M hydrochloric acid and 380 mL of distilled water.Put the sodium nitrite (44.2 g, 0.641 mol) at 0 was dissolved in 220 mL of distilled water, slowly added dropwise and stirred for 1 hour. Potassium iodide was dissolved in 850 mL of distilled water, slowly added dropwise, and stirred at room temperature for 1 hour. The temperature was raised to 60 C. and stirred for 3 hours. Extracted with ethyl acetate and separated by column chromatography to obtain [Intermediate 5-c] 42.1 g (yield 29%).
29.1% 4,4'-dibromo-2,2'-diaminobiphenyl87.7 g (0.256 mol), 380 mL 12 M HCl,380 mL of water was added. The temperature of the reactor was lowered to 0 C.44.2 g (0.641 mol) of sodiumnitrite was dissolved in 220 mL of water and slowly added dropwise to the reactor,When the dropwise addition was completed, the mixture was stirred for 1 hour at the same temperature for 1 hour. Potassium iodide was dissolved in 850 mL of water and slowly added dropwise.When the dropwise addition was completed, the mixture was stirred at room temperature for 1 hour. And the temperature of the reactor was raised to 60 C. and stirred for 3 hours.When the reaction was completed, the mixture was lowered to room temperature and extracted using Ethylacetate to separate the organic layer.The separated organic layer was dried by anhydrous treatment, and then separated by column chromatography using hexane as a developing solvent.42.1 g (29.1%) of 4,4'-dibromo-2,2'-diiodobiphenyl was obtained.
27% Step ^ - Preparation of Compound Int-43bTo a stirred suspension of 2,2'-diamino-4,4'-dibromobiphenyl Int-43a (11.2 g, 33 mmol) (prepared from J. Am. Chem. Soc. 2005, 127, 7662) in cone. HC1 (50 mL)/water (50 mL) at 0 C was added a 50% soln of NaN02 in water (30 mL, 73 mmol) over 30 minutes while maintaining the temperature <5 C. The mixture was allowed to stir for an additional 30 minutes whereupon a soln of KI (54 g, 0.33 mol) in water (120 mL) was added dropwise over 1 h. The resulting mixture was heated to 60 C and was allowed to stir for 5h. The mixture was cooled to room temperature and was filtered. The resultant solid was washed with EtOAc (~ 500 mL) and the resultant filtrate was washed with brine (2 x 50 mL), dried (Na2S04), filtered, and concentrated in vacuo. The crude product was purified using flash chromatography using 100% hexanes to provide 5.1 g (27%) of compound Int-43b as a colorless oil.
25% With toluene-4-sulfonic acid; potassium iodide; sodium nitrite; In water; acetonitrile; at 20℃;Inert atmosphere; (3) The compound 3 (7.16 g, 20 mmol) and p-toluenesulfonic acid (17.18 g, 90.4 mmol) were dissolved in 200 mL of acetonitrile, stirred at 0 C for half an hour, and sodium nitrite (4.14, 1) and potassium iodide (12.45 g, 75 mmol) were dissolved in 40 mL of water and added dropwise to the reaction flask with a constant pressure dropping funnel, which was then allowed to warm to room temperature and allowed to react overnight. After completion of the reaction, the saturated sodium thiosulfate solution was added to the reaction solution and the resulting iodine was extracted and extracted with methylene chloride. The organic phase was collected and dried over anhydrous sodium sulfate. The product was purified by silica gel chromatography using petroleum ether as eluent The residue was purified by column chromatography and dried in vacuo to give a white solid 4 in a yield of 25%
23% 4,4'-Dibromo-1,1'-biphenyl-2,2'-diamine(16g, 46.8 mmol) dissolved in a mixture of 56 mL hydrochloric acid and 64 mL water.Stir under ice bath. after that,An aqueous solution of 40 mL of sodium nitrite (8 g, 116 mmol) was slowly added dropwise to the reaction solution, and the temperature was constant at about 0 C during the dropwise addition. After the addition is completed,The mixture was stirred for 30 minutes, and an aqueous solution of potassium iodide (77 g dissolved in 150 mL of water) was added dropwise to the reaction solution at -5 C.After the reaction at room temperature for 1 hour, the temperature was raised to 60 C for 3 hours.The solution turned dark brown. After the reaction is completed, the reaction solution is suction filtered.Purified by column chromatography (silica gel, n-hexane) to give a white solid(6.07g, 23%).
18% To a mixture of 4,4'-Dibromobiphenyl-2,2'-diamine (1.8 g, 4.5 mmol) and 8 N HCl aqueous solution (35 mL), an aqueous solution of sodium nitrite (0.7 g, 10.1 mmol) was added dropwise at 0 C. After stirring for 30 min, a solution of KI (1.6 g, 9.6 mmol) in water (5 ml) was slowly added during 5 min. Then, the mixture was warmed up to room temperature for 1 h. The mixture was extracted with CH2Cl2 (3×30 mL). The organic phase was washed with saturated sodium thiosulfate solutionan and water, and dried over anhydrous Na2SO4. After concentrated under vacuum, the crude product was purified by column chromatography silica gel with petroleum ether to get white solid (0.5 g, 18%). 1H NMR (400 MHz, CDCl3): 8.09 (d, J = 2.0 Hz, 2H), 7.55 (dd, J = 8.4, 2.0 Hz, 2H), 7.03 (d, J = 8.0 Hz, 2H).
To 36% hydrochloric acid/water (75 ml/85 ml) was added 21.3 g of the compound (10-c), and to this, an aqueous NaNO2 solution (NaNO2 10.7 g/water 55 ml) was added dropwise at 5C. The resulting mixture was stirred at 5C for 30 minutes, and then an aqueous KI solution (KI 104 g/water 200 ml) was added dropwise and the resulting mixture was stirred at 5C for 1 hour, at room temperature for 1 hour and at 60C for 3 hours. A solid fraction produced was collected by filtration and purified by column chromatography (filler: silica gel, eluent: hexane) to obtain 4.27 g of compound (10-d).

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