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Chemical Structure| 25148-68-9 Chemical Structure| 25148-68-9

Structure of 25148-68-9

Chemical Structure| 25148-68-9

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Product Citations

Product Citations

Andressa V. Müller ; Shahbaz Ahmad ; Jake T. Sirlin ; Mehmed Z. Ertem ; Dmitry E. Polyansky ; David C. Grills , et al.

Abstract: The reaction steps for the selective conversion of a carbonyl complex to a hydroxymethyl complex that releases methanol upon irradiation with visible light have been successfully quantified in solution with dihydrobenzimidazole organic hydride reductants. Dihydrobenzimidazole reductants have been shown to be inactive toward H2 generation in the presence of a wide range of proton sources and have been regenerated electrochemically or photochemically. Specifically, the reaction of cis-[Ru(bpy)2(CO)2]2+ (bpy = 2,2′-bipyridine) with one equivalent of a dihydrobenzimidazole quantitatively yields a formyl complex, cis-[Ru(bpy)2(CO)(CHO)]+, and the corresponding benzimidazolium on a seconds time scale. Kinetic experiments revealed a first-order dependence on the hydride concentration and an unusually large kinetic isotope effect, inconsistent with direct hydride transfer and more likely to occur by an electron transfer-proton-coupled electron transfer (EΤ−PCET) or related mechanism. Further reduction/protonation of cis-[Ru(bpy)2(CO)(CHO)]+ with two equivalents of the organic hydride yields the hydroxymethyl complex cis-[Ru(bpy)2(CO)(CH2OH)]+. Visible light excitation of cis-[Ru(bpy)2(CO)(CH2OH)]+ in the presence of excess organic hydride was shown to yield free methanol. Identification and quantification of methanol as the sole CO product was confirmed by 1H NMR spectroscopy and gas chromatography. The high selectivity and mild reaction conditions suggest a viable approach for methanol production from CO, and from CO2 through cascade catalysis, with renewable organic hydrides that bear similarities to Nature’s NADPH/NADP+.

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Product Details of [ 25148-68-9 ]

CAS No. :25148-68-9
Formula : C7H12Cl2N2
M.W : 195.09
SMILES Code : NC1=CC=CC=C1NC.[H]Cl.[H]Cl
MDL No. :MFCD00042021
InChI Key :DKEONVNYXODZRQ-UHFFFAOYSA-N
Pubchem ID :91296

Safety of [ 25148-68-9 ]

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

Computational Chemistry of [ 25148-68-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 0.0
Num. H-bond donors 2.0
Molar Refractivity 54.08
TPSA ?

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

38.05 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

2.83
Log Po/w (WLOGP)?

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

2.73
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.

1.8
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

0.81
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.63

Water Solubility

Log S (ESOL):?

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

-3.17
Solubility 0.132 mg/ml ; 0.000676 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.

-3.29
Solubility 0.101 mg/ml ; 0.000516 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

-2.43
Solubility 0.725 mg/ml ; 0.00372 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.

-5.48 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<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)

1.0

Application In Synthesis of [ 25148-68-9 ]

* 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 [ 25148-68-9 ]

[ 25148-68-9 ] Synthesis Path-Downstream   1~3

  • 2
  • [ 25148-68-9 ]
  • [ 152628-03-0 ]
  • [ 152628-02-9 ]
YieldReaction ConditionsOperation in experiment
93% With methanesulfonic acid; In i-Amyl alcohol; at 130 - 135℃; for 18h; 1.2 kg of isoamyl alcohol was added to the reaction flask.Add <strong>[152628-03-0]2-n-propyl-4-methyl-6-carboxybenzimidazole</strong> (400 g, 1.83 mol) and stir.Methanesulfonic acid (176 g, 1.83 mol, 1.0 eq) was added and N-methyl-phenylenediamine hydrochloride (360 g, 1.85 mol) was added.The temperature was raised to 130-135 C to reflux and the reaction was carried out for at least 18 hours until no significant moisture was separated. After the reaction is completed, cool to about 70 C,Add 2000 ml of water, stir, adjust the pH to 6~7 with 30% NaOH solution, stir and cool to 20~25 C after completion, and filter to obtain the product, the yield is 93.0%, and the HPLC purity is 99.6%.
77.4% 4-Methyl-2-n-propyl-lH-benzimidazole-6-carboxylic acid (50 gms) is suspended in Poly phosphoric acid (300 gms), temperature is raised and maintained for 30 min at 70 - 750C, N-Methyl-o-phenylenediamine dihydrochloride. (45 gms) is added lot wise over 2 hrs and maintained at temperature of 70 - 750C for lhr. The temperature of the reaction mass is raised and maintained for 10 hrs at 130 - 1350C. Mass temperature is cooled to 7O0C, water (600 ml) is added slowly at temperature of 60 - 9O0C. Temperature of the reaction mass is cooled to 3O0C, pH is adjusted to 8.0 - 8.5 with aqueous ammonia solution. EPO <DP n="12"/>Temperature of the reaction mass is raised, maintained at 50- 550C for 1 hr, filter the solid, wet cake is washed with hot water (200 ml) and unload the wet cake. The above wet cake suspended in water (900 ml), temperature is raised and mixed for 1 hr at 50 - 550C. Filtered the solid, washed with hot water (100 ml) and dried the wet cake at temperature of 70 - 750C till constant weight. The above dry material is suspended in methanol (260 ml), and temperature is raised to 45 - 5O0C, charcoal (6.5 gms) is added and mixed for about 30 min. Insolubles are filtered through hyflow bed, washed the bed with hot methanol (60 ml), collect and cooled the filtrate to 250C. Water (160 ml) is added slowly to the filtrate at temperature of 25 - 350C, Mass temperature is raised, maintained for 1 hr at reflux temperature. Reaction mass temperature is cooled, maintained for 2 hrs at 0 - 50C. The solid obtained is filtered, wet cake is washed with methanol (60 ml), the wet cake is dried at temperature of 70 - 750C till becomes constant weight. The dry weight of 4-Methyl-6(l -methyl benzimidazol-2-yl)-2-n-propyl IH- benzimidazole is 54 gms (Yield 77.4%). Water content by KF is 5.85%.
With polyphosphoric acid; at 150℃; for 14h; General procedure: A solution of an appropriate ester (25.01mmol) in methanol (25mL) was added to a solution of NaOH (2.0g) in water (25mL), and the mixture was heated under reflux for 2h. After evaporation of methanol, the pH was adjusted to 4-5 by addition of aqueous citric acid. The precipitated solid was filtered, washed with ethanol and dried to yield carboxylic acid. The resulting compound was dissolved in polyphosphoric acid (10mL) at 150C. N-Methyl-o-phenylenediamine dihydrochloride (3.65g, 18.8mmol) was added to the mixture for 4 times in 4h. After stirring at 150C for 10h, the mixture was cooled and then poured into ice water (30mL). The pH was adjusted to 10 by addition of concentrated ammonia (ice cooling). The precipitated solid was filtered off, dried, and boiled in ethyl acetate (300mL). After cooling, the precipitated solid was filtered off, washed with diethyl ether, and dried to give the product as white solid.4.1.2.3 2-Propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (8c) [14] 8c was prepared by following the above general procedure. Yield: 60.1%. MP: 193-195 C. 1H NMR (400 MHz, CDCl3) delta: 7.82 (d, 2H), 7.30-7.53 (m, 4H), 3.95 (s, 3H), 2.89 (t, 2H), 2.61 (s, 3H), 1.79 (m, 2H), 0.91 (t, 3H). MS (ESI): [M + H]+ calcd 305.2; found 305.1.
  • 3
  • [ 25148-68-9 ]
  • [ 4865-84-3 ]
  • [ 854019-04-8 ]
 

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