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Structure of 4856-97-7

Chemical Structure| 4856-97-7

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Product Details of [ 4856-97-7 ]

CAS No. :4856-97-7
Formula : C8H8N2O
M.W : 148.16
SMILES Code : C1=CC=CC2=C1[NH]C(=N2)CO
MDL No. :MFCD00014560
InChI Key :IAJLTMBBAVVMQO-UHFFFAOYSA-N
Pubchem ID :78569

Safety of [ 4856-97-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 4856-97-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 9
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 42.22
TPSA ?

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

48.91 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.16
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

0.73
Log Po/w (WLOGP)?

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

0.9
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.

0.44
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

1.87
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.02

Water Solubility

Log S (ESOL):?

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

-1.76
Solubility 2.59 mg/ml ; 0.0175 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.

-1.34
Solubility 6.84 mg/ml ; 0.0461 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

-2.72
Solubility 0.282 mg/ml ; 0.00191 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

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.

-6.69 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)

1.47

Application In Synthesis of [ 4856-97-7 ]

* 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 [ 4856-97-7 ]

[ 4856-97-7 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 4856-97-7 ]
  • [ 3314-30-5 ]
YieldReaction ConditionsOperation in experiment
85% With manganese(IV) oxide; In dichloromethane; at 40℃; for 2h; To a solution of 1 (5.0 g, 34 mmol) in DCM was added MnO2(1.3 g, 6.8 mmol). The resulting solution was stirred at 40 C for 2 h and monitored by TLC. Aftercomplete conversion of starting material, reaction mixture was cooled to room temperature, filteredand concentrated in vacuo to obtain 2 as white solid in 85.0% yield. LC-MS m/z: 147.1 [M + H]+.
70% With [Ru(2,6-bis[1-(pyridin-2-yl)-1H-benzo[d]-imidazol-2-yl]pyridine)(pyridine-2,6-dicarboxylate)]; dihydrogen peroxide; In water; at 50℃; for 5.5h;Catalytic behavior; The procedure for gram scale oxidation of (1H-benzo[d]imidazol-2-yl)methanol to 1H-benzo[d]imidazole-2-carbaldehydewas as follows: (1H-benzo[d]imidazol-2-yl)methanol (0.1 mol,14.8 g) and [Ru(bpbp)(pydic)] (0.001 mmol, 7.32 × 10-3 g) wereadded into a reactor. The reactor containing this mixture was heatedto 50 C in an oil bath under vigorous stirring and then 30% H2O2(30 mL, 0.3 mol) was slowly dropwise over a period of 30 min. The mixture was stirred for 5 h. After filtering, the solution wasevaporation under reduced pressure at 50 C. Pure 1H-benzo[d]imidazole-2-carbaldehyde (0.07 mmol, 10.2 g) was obtained with ayield of 70% after recrystallisation from 30% H2SO4 solution. Theproduct, 1H-benzo[d]imidazole-2-carbaldehyde, was identified byits 1H NMR spectrum.
57% With Ru(bpp)(pydic); dihydrogen peroxide; at 50℃; The method for synthesizing 2-aldehyde benzimidazole in this example is as follows2-Hydroxymethylbenzimidazole (0.1 mol, 14.8 g)The rhodium complex (10-4 mol, 0.0577 g) in Example 1 was added to the reaction vessel.Hydrogen peroxide (30%, 0.3 mol, 9.1 ml) was slowly added to the reaction vessel with stirring.The reaction temperature was controlled at 50C for several hours.The reaction solution was concentrated under reduced pressure,Obtain a solid product,The solid product was dissolved in dichloromethane and subjected to silica gel column chromatography.Get pure product2-aldehyde benzoimidazole 8.32 g,Yield 57%.
51% With manganese(IV) oxide; In methanol; dichloromethane; General procedure: To a stirred solution of the (1H-benzo[d]imidazol-2-yl)methanol from above (2.6 mmol) in dryCH2Cl2/MeOH (6:1, 3.5 mL) was added activated manganese dioxide (85% purity, <5 micron, 2.328 g, 22.8 mmol)and the suspension stirred overnight, at which point the black slurry was filtered through a cake of celite andwashed with MeOH (3x5 mL). The combined washings were concentrated to afford a dark brown solid.Purification of the crude product by column chromatography on silica gel (CH2Cl2:MeOH, 98:2 to 95:5) affordedthe title compound 1H-benzo[d]imidazole-2-carbaldehyde (2i) (0.245 g, 51%).
With manganese(IV) oxide; In ethyl acetate; at 65℃; for 1h; General procedure: A solution of 2a-2d (2 mmol), MnO2 (3.48 g, 40 mmol) was added to EtOAc (120 mL), then refluxedat 65 C for 1 h (monitored by TLC). Afterwards the solution was filtered, and concentrated in vacuoto give pure compounds 3a-3d (in 60%-76% yield) [17].
With manganese(IV) oxide; In dichloromethane; at 40℃; for 2h; The resulting solid (1H-benzimidazol-2-yl) methanol (34 mmol) was dissolved in 250 mL of dichloromethane and stirredFollowed by addition of manganese dioxide (0.68 mmol). The temperature was raised to 40 C and stirring was continued for 2 hours to monitor the reaction. After the reaction is complete, the product is evaporated to drynessDichloromethane, 150 mL of tetrahydrofuran was added. Directly to the next step
With manganese dioxide; In N-methyl-acetamide; ethanol; EXAMPLE I STR28 A mixture of 2-Hydroxymethyl-benzimidazole (11.9 g) and MnO2 (59.5 g) in ethanol (250 mL) was vigorously stirred for 2 days. The reaction was concentrated in vacuo, hot dimethylformamide was added and the mixture was filtered through celite. After removal of the solvent in vacuo the tan solid was triturated with ethanol to afford 2-Benzimidazolecarboxaldehyde as a tan powder.

  • 2
  • [ 4856-97-7 ]
  • [ 10406-06-1 ]
  • (1H-benzoimidazol-2-yl)methyl 5-bromo-1H-indole-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% General procedure: One of compounds 4a-4f (5 mmol) was dissolved in THF (25 mL) and DCC (1.24 g, 6 mmol), and DMAP (0.12 g, 1 mmol) was slowly added and the mixture was stirred for 30 min. Compounds 2a-2c (5 mmol) was added and the mixture was stirred for 7-9 h. The by-product, N,N'-dicyclohexylurea, was removed by filtration. The filtrate was concentrated in vacuum to give a solid which was dissolved in CH2Cl2 and the product 5a-5n was filtered off.
85.95% To a three-necked flask was added 1.24 g (6 mmol) of dicyclohexylcarbodiimide, 0.12 g (1 mmol) of 4-dimethylaminopyridine was added, followed by addition of 25 mL of tetrahydrofuran. After stirring, 1.20 g of <strong>[10406-06-1]5-bromoindole-3-carboxylic acid</strong> (5 mmol) was added and stirred at room temperature for half an hour. 75 g (5 mmol) 2-hydroxymethyl benzimidazole, And then stirred at room temperature for 8h, stop the reaction, filtration, steaming the filtrate, drying, and then dissolved in methylene chloride, room temperature conditions, standing until a large amount of soil precipitation precipitate, filter, filter cake, vacuum drying 1.59g(1H-benzimidazol-2-yl) methyl-5-bromo-1H-indole-3-carboxylate in a yield of 85. 95%.
  • 3
  • [ 4856-97-7 ]
  • [ 63176-44-3 ]
  • (1H-benzoimidazol-2-yl)methyl 2-methyl-1H-indole-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
22% General procedure: One of compounds 4a-4f (5 mmol) was dissolved in THF (25 mL) and DCC (1.24 g, 6 mmol), and DMAP (0.12 g, 1 mmol) was slowly added and the mixture was stirred for 30 min. Compounds 2a-2c (5 mmol) was added and the mixture was stirred for 7-9 h. The by-product, N,N'-dicyclohexylurea, was removed by filtration. The filtrate was concentrated in vacuum to give a solid which was dissolved in CH2Cl2 and the product 5a-5n was filtered off.
 

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