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Chemical Structure| 78581-99-4 Chemical Structure| 78581-99-4

Structure of 78581-99-4

Chemical Structure| 78581-99-4

5,6-Difluorobenzimidazole

CAS No.: 78581-99-4

4.5 *For Research Use Only !

Cat. No.: A202173 Purity: 95%

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Product Details of [ 78581-99-4 ]

CAS No. :78581-99-4
Formula : C7H4F2N2
M.W : 154.12
SMILES Code : FC1=C(F)C=C2N=CNC2=C1
MDL No. :MFCD02031530
InChI Key :IAYQNPPZFVAZLY-UHFFFAOYSA-N
Pubchem ID :345375

Safety of [ 78581-99-4 ]

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

Computational Chemistry of [ 78581-99-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 36.01
TPSA ?

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

28.68 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.07
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

1.69
Log Po/w (WLOGP)?

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

2.68
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.

1.85
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

2.87
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.03

Water Solubility

Log S (ESOL):?

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

-2.47
Solubility 0.527 mg/ml ; 0.00342 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.

-1.91
Solubility 1.91 mg/ml ; 0.0124 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

-3.45
Solubility 0.0543 mg/ml ; 0.000352 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.

-6.04 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)

1.65

Application In Synthesis of [ 78581-99-4 ]

* 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 [ 78581-99-4 ]

[ 78581-99-4 ] Synthesis Path-Downstream   1~34

  • 1
  • [ 67525-66-0 ]
  • [ 78581-99-4 ]
  • [ 78582-01-1 ]
  • 2
  • [ 961-07-9 ]
  • [ 78581-99-4 ]
  • (2R,3S,5R)-5-(5,6-Difluoro-benzoimidazol-1-yl)-2-hydroxymethyl-tetrahydro-furan-3-ol [ No CAS ]
  • 3
  • [ 78581-99-4 ]
  • [ 118-00-3 ]
  • [ 78582-01-1 ]
  • 4
  • [ 109-65-9 ]
  • [ 78581-99-4 ]
  • 5,6-difluoro-N,N'-dibutylbenzimidazolium bromide [ No CAS ]
  • 5
  • [ 64-18-6 ]
  • [ 76179-40-3 ]
  • [ 78581-99-4 ]
YieldReaction ConditionsOperation in experiment
88% at 80℃; for 12h; A solution of 4,5-difluorobenzene-1 ,2-diamine (1.5 g, 10 mmol) in formic acid (20 mL) was heated at 80C for 12 hours. The reaction mixture was cooled to 25C and concentrated under reduced pressure. The residue was recrystallized form Petroleum ether:EtOAc (15: 1 ) to afford 5,6-difluoro- 1 H-benzo[d]imidazole as a yellow solid (1.4 g, 88%). MS (ESI) m/z: 155 [M+H]+.
75% With orthoformic acid triethyl ester; at 100℃; for 1h; Step 2: A stirred mixture of 4,5-difluorobenzene-1,2-diamine (1.40 g, 9.7 mmol) from the previous step, formicacid (2.0 mL), and triethyl orthoformate (20 mL) was heated at 100 C for 1 h. The reaction mixture was cooled to rt andconcentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 5%MeOH in DCM to afford 5,6-difluoro-1H-benzo[d]imidazole as (1.12 g, 75%) as a white solid. 1H NMR (300 MHz, CDCl3) delta 8.07 (s, 1H), 7.44 (m, 2H); LCMS (ESI) m/z 155 (M + H)+.
  • 6
  • [ 76513-69-4 ]
  • [ 78581-99-4 ]
  • 5,6-difluoro-2-(2-trimethylsilanyl-ethoxymethyl)-1<i>H</i>-benzoimidazole [ No CAS ]
  • 7
  • [ 95201-94-8 ]
  • [ 78581-99-4 ]
  • [ 959999-85-0 ]
YieldReaction ConditionsOperation in experiment
With 1-methyl-1H-imidazole; sodium hydrogencarbonate; In chloroform; at 55℃; for 24h; Step A-Methyl 5-(5,6-difluoro-1H-benzimidazol-1-yl)-3-hydroxy-2-thiophenecarboxylate To a mixture of 5,6-difiuoro-1H-benzimidazole (0.5 g, 3.2 mmol) and 2-chloro-3-oxo-2,3-dihydro-2-thiophenecarboxylate (0.72 g, 3.7 mmol) in 10 mL of CHCl3 was added N-methylimidazole (0.4 g, 4.9 mmol) and NaHCO3 (0.82 g, 9.7 mmol). The mixture was heated to 55 C. for 24 h. Silica gel (2 g) was added and the volatiies were evaporated under reduced pressure and the residue was purified by flash column chromatography (0 to 50% EtOAc:DCM) to afford 0.71 g of the titled compound. MS (ESI): 311 [M+H]+.
With 1-methyl-1H-imidazole; sodium hydrogencarbonate; In chloroform; at 55℃; for 24h; 27: Methyi 3-[(1 /?)-1-(2-chioro-3-hydroxyphenvi)ethv?oxv}-5- (5.6-dif iuoro-1 MbenzimidazoS-1 -yl)-2-thiophenecarboxyiateStep A - Methyl 5-{5,6-dif.uoro-1 Mbe?zimidazoi-1-yl)~3-hydroxy~2- thiophe?ecarboxylate <n="120"/>To a mixture of 5,6-dif.upsilonoro-1 Mbenzsmidazoie (0.5 g, 3.2 rnmol) and 2-chioro- 3-oxo-2,3~dihydro~2-thiophenecarboxyiate (0.72 g, 3.7 mrnof) in 10 mL of CHCI3 was added Mmefhyiimidazole (0.4 g, 4.9 mrnol) and NaHCO3 (0.82 g, 5 9.7 mmol). The mixture was heated to 550C for 24 h. Silica gel (2 g) was added and the voiatites were evaporated under reduced pressure and the residue was purified by flash column chromatography (0 to 50% EtOAc: DCIVI) to afford 0.71 g of the tilted compound, MS (ESI): 311 [M+H]*.
  • 8
  • [ 78581-99-4 ]
  • 2-[(4-bromo-phenyl)-piperidin-4-ylidene-methyl]-5,6-difluoro-1<i>H</i>-benzoimidazole [ No CAS ]
  • 9
  • [ 78581-99-4 ]
  • 4-[(4-bromo-phenyl)-chloro-(5,6-difluoro-1<i>H</i>-benzoimidazol-2-yl)-methyl]-piperidine-1-carboxylic acid <i>tert</i>-butyl ester [ No CAS ]
  • 13
  • [ 78581-99-4 ]
  • 4'-[(1-cyclopropylmethyl-piperidin-4-ylidene)-(5,6-difluoro-1<i>H</i>-benzoimidazol-2-yl)-methyl]-biphenyl-3-carbonitrile [ No CAS ]
  • 14
  • [ 78581-99-4 ]
  • 5,6-Difluoro-1-β-D-ribofuranosylbenzimidazole 3',5'-phosphate [ No CAS ]
  • 16
  • [ 3764-01-0 ]
  • [ 78581-99-4 ]
  • [ 741290-21-1 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In dimethyl sulfoxide; at 40℃; for 17h; A solution OF 2, 4, 6-TRICHLOROPYRIMIDIN (4.2 gram), <strong>[78581-99-4]5,6-difluorobenzimidazole</strong> (3.6 gram) and K2CO3 (6.4 gram) in dimethyl sulfoxide (150 ml) was stirred at 40 C for 17 hours. The solution was taken up in water, and extracted three times with ethyl acetate. The ethyl acetate layers were combined, washed with brine, dried over magnesium sulfate, filtered, and the solvents were removed in vacuo. Silica gel chromatography (heptane/ethyl acetate 9/1) provided 1.2 g of the title compound.
  • 17
  • [ 76179-40-3 ]
  • [ 123-06-8 ]
  • [ 78581-99-4 ]
YieldReaction ConditionsOperation in experiment
In isopropyl alcohol; for 16h;Heating / reflux; Example 4: Synthesis of 5,6-Difluoro-lH-benzo[d]imidazole EPO <DP n="31"/>EtOCH=C(CN)2 iPrOH [0088] A solution of 4,5-difluoro-2-nitroaniline (6)(1.0 g) in 30 niL of THF was treated with a solution comprised of 6 g OfNa2S2O4 and 3 g NaHCO3 in 30 niL of water. Methanol (10 mL) was added after the addition of the aqueous solution so that the mixture remained homogeneous. The mixture was stirred for two hours and then diluted with 100 mL of ethyl acetate and 100 mL of water. The organic layer was separated and the aqueous layer was extracted again with 100 mL of methylene chloride. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to provide the crude intermediate 4,5-difluorobenzene-l,2-diamine (7). The intermediate was refluxed with (ethoxymethylene)malononitrile (1.1 g) in 25 mL of isopropyl alcohol for 16 h. The mixture was concentrated in vacuo and the resulting crude product was suspended in water and filtered. The precipitate was washed with water and air-dried to provide 380 mg of 5,6-difluoro-lH-benzo[d]imidazole (8).
In isopropyl alcohol; for 16h;Heating / reflux; Example 4 Synthesis of 5,6-Difluoro-1H-benzo[d]imidazole A solution of 4,5-difluoro-2-nitroaniline (6)(1.0 g) in 30 mL of THF was treated with a solution comprised of 6 g of Na2S2O4 and 3 g NaHCO3 in 30 mL of water. Methanol (10 mL) was added after the addition of the aqueous solution so that the mixture remained homogeneous. The mixture was stirred for two hours and then diluted with 100 mL of ethyl acetate and 100 mL of water. The organic layer was separated and the aqueous layer was extracted again with 100 mL of methylene chloride. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to provide the crude intermediate 4,5-difluorobenzene-1,2-diamine (7). The intermediate was refluxed with (ethoxymethylene)malononitrile (1.1 g) in 25 mL of isopropyl alcohol for 16 h. The mixture was concentrated in vacuo and the resulting crude product was suspended in water and filtered. The precipitate was washed with water and air-dried to provide 380 mg of 5,6-difluoro-1H-benzo[d]imidazole (8).
In isopropyl alcohol; for 16h;Heating / reflux; A solution of 4,5-difluoro-2-nitroaniline (6)(1.0 g) in 30 mL of THF was treated with a solution comprised of 6 g OfNa2SaO4 and 3 g NaHCC>3 in 30 mL of water. Methanol (10 mL) was added after the addition of the aqueous solution so that the mixture remained homogeneous. The mixture was stirred for two hours and then diluted with 100 mL of <n="29"/>ethyl acetate and 100 mL of water. The organic layer was separated and the aqueous layer was extracted again with 100 mL of methylene chloride. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to provide the crude intermediate 4,5-difluorobenzene-l,2-diamine (7). The intermediate was refluxed with (ethoxymethylene)malononitrile (1.1 g) in 25 mL of isopropyl alcohol for 16 h. The mixture was concentrated in vacuo and the resulting crude product was suspended in water and filtered. The precipitate was washed with water and air-dried to provide 380 mg of 5,6- difluoro-lH-benzo[d]imidazole (8).
  • 18
  • [ 10416-59-8 ]
  • [ 78581-99-4 ]
  • C10H12F2N2Si [ No CAS ]
  • 21
  • [ 76179-40-3 ]
  • [ 122-51-0 ]
  • [ 78581-99-4 ]
  • 22
  • α-D-ribofuranose-1-phosphate [ No CAS ]
  • [ 78581-99-4 ]
  • [ 78582-01-1 ]
  • 23
  • 2-deoxy-α-D-ribofuranose-1-phosphate [ No CAS ]
  • [ 78581-99-4 ]
  • (2R,3S,5R)-5-(5,6-Difluoro-benzoimidazol-1-yl)-2-hydroxymethyl-tetrahydro-furan-3-ol [ No CAS ]
  • 25
  • [ 78581-99-4 ]
  • [ 89892-38-6 ]
  • 2-bromo-4-((5,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
39% With potassium carbonate; In acetonitrile; at 25℃; for 12h; A solution of 5,6-difluoro-1 H-benzo[d]imidazole (1.4 g, 9 mmol), 2-bromo-4-(bromomethyl) benzonitrile (2.5 g, 9 mmol) [see Example 1 Step A] and K2C03 (3.8 g, 27 mmol) in CH3CN (50 mL) was heated at 25C for 12 hours. The reaction mixture was cooled to 25C, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography using Petroleum ether:EtOAc (30: 1-3:1 ) as eluting solvents to afford 2-bromo-4-((5,6-difluoro-1 H- benzo[d]imidazol-1-yl)methyl)benzonitrile as a yellow solid (1.3 g, 39%). MS (ESI) m/z: 348 [M+H]+.
  • 26
  • [ 78581-99-4 ]
  • 6-((5,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylsulfinyl)benzo[d]thiazole [ No CAS ]
  • 27
  • [ 78581-99-4 ]
  • (1R,2R)-2-((6-((5,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol [ No CAS ]
  • 28
  • 6-(chloromethyl)-2-(methylthio)benzo[d]thiazole [ No CAS ]
  • [ 78581-99-4 ]
  • 6-((5,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylthio)benzo[d]thiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% Step 3: To a stirred mixture of sodium hydride (60% dispersion in mineral oil, 0.144 g, 3.0 mmol) in anhydrousDMF (10 mL) at 0 C under a nitrogen atmosphere was added portionwise 6-difluoro-1H-benzo[d]imidazole (0.475 g,2.0 mmol) from the previous step. The mixture was stirred at 0 C for 5 min. To the mixture was added dropwise asolution of 6-(chloromethyl)-2-(methylthio)benzo[d]thiazole (0.32 g, 2.0 mmol) from Step 4 of Example 36 in anhydrousDMF (2 mL). The reaction mixture was allowed to warm to rt and stir for 1 h. The mixture was poured into ice-water andextracted with EtOAc (100 mL 3 2). The combined organic layers were further washed with water (20 mL) then brine(20 mL). The organic layer was separated and dried over Na2SO4, filtered, and concentrated under reduced pressureto afford 6-((5,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylthio)benzo[d]thiazole (0.55 g, 76%) as a yellow solid,which was not purified further. 1H NMR (300 MHz, CDCl3) delta 7.97 (s, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.59 (m, 1H), 7.50(s, 1H), 7.24 (m, 1H), 7.02 (m, 1H), 5.40 (s, 2H), 2.78 (s, 3H); LCMS (ESI) m/z 348 (M + H)+.
  • 29
  • [ 512776-95-3 ]
  • [ 78581-99-4 ]
  • (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)-2-hydroxy-2-methylpropionamide [ No CAS ]
  • (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(5,6-difluoro-1H-benzo[d]imidazol-2-yl)-2-hydroxy-2-methylpropanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a solution of <strong>[78581-99-4]5,6-difluoro-1H-benzoimidazole</strong> (0.23 g, 0.00148 mol) in anhydrous THF (10 mL), which was cooled in an dry-ice acetone bath under an argon atmosphere, was added LDA (2.0 M in THF, 1.11 mL, 0.0022 mol). After addition, the resulting mixture was stirred for 2 h. (S)-N-(4-Cyano-3-(trifluoromethyl)phenyl)-2-methyloxirane-2-carboxamide (0.40 g, 0.00148 mol) was added to above solution, and the resulting reaction mixture was allowed to stir overnight at room temperature under argon. The reaction was quenched by water, extracted with ethyl acetate. The organic layer was dried with MgSO4, filtered, and concentrated under vacuum. The product was purified by a silicon gel column using methylene chloride and methanol (19:1) as eluent to afford the desired compound as white solid.[00364] (S)-N-(4-Cyano-3-trifluoromethyl-phenyl)-3-(5,6-difluoro-benzoimidazol-1-yl)-2- hydroxy-2-methyl-propionamide (C19H13F5N4O2) (73)
  • 30
  • [ 76179-40-3 ]
  • [ 68-12-2 ]
  • [ 78581-99-4 ]
YieldReaction ConditionsOperation in experiment
58% With phenylsilane; at 120℃; for 12h; General procedure: A mixture of 1a (1b-1n, 0.4 mmol) and PhSiH3 (98 mL, 1.6 mmol)in N,N-dimethylformamide 2a (2b-2c, 1 mL) was stirred at 120 C for 12 h. When the reaction was completed, the resulting mixture was extracted with ethyl acetate three times. The combined organic layer was washed by NaCl aqueous solution and dried over anhydrous Na2SO4, after which the solvent was removed under reduced pressure. The residue was purified by column chromatography onsilica gel with petroleum ether and ethyl acetate (6:1-1:2) to give the corresponding product 3a (3b-3p).
  • 31
  • [ 603-76-9 ]
  • [ 215734-58-0 ]
  • 6,7-difluoro-2-(1-methyl-1H-indol-3-yl)quinoxaline [ No CAS ]
  • [ 78581-99-4 ]
  • [ 27065-95-8 ]
YieldReaction ConditionsOperation in experiment
36%; 12% With acetic acid; at 110℃; for 35h; Compound 1 (0.225 g, 1.35 mmol) was heated with1-methylindole (0.5 g, 3.8 mmol) in AcOH (3 mL) at 110C for 35 h, cooled, and stored at 20-25 for 12 h. The resultingprecipitate was filtered off and recrystallized from DMF. Yield of tris(1-methylindol-3-yl)methane (4a), 0.060 g (12%),mp 241-243C [6]. The PMR spectrum was published [6]. Mass spectrum (EI, 70 eV), m/z (Irel, %): 404 (29), 403 (M+, 100),402 (44), 272 (75), 271 (85), 257 (15).
  • 32
  • [ 95-20-5 ]
  • [ 215734-58-0 ]
  • 6,7-difluoro-2-(2-methyl-1H-indol-3-yl)quinoxaline [ No CAS ]
  • [ 602-04-0 ]
  • [ 78581-99-4 ]
YieldReaction ConditionsOperation in experiment
25%; 9% With acetic acid; at 110℃; for 35h; The reaction mixturewas evaporated in vacuo. The solid was worked up with EtOH (3-4 mL). The precipitate of tris(2-methylindol-3-yl)methane(4b) was filtered off and rinsed with EtOH. Yield 9%, mp > 300 (lit. [7] mp > 300). 1 NMR spectrum (400 MHz,DMSO-d6, , ppm, J/Hz): 1.92 (9, s, CH3), 6.09 (1, s, CH), 6.60 (3, ddd, J = 7.9, 7.2, 1.0, H-5), 6.84-6.90 (6, m,H-6, 7), 7.16 (3, dd, J = 7.9, 1.2, H-4), 10.37 (3, s, NH). Mass spectrum (EI, 70 eV), m/z (Irel, %): 404 (33), 403 (M+, 89),402 (22), 272 (75), 271 (15), 257 (86), 256 (32).
  • 33
  • C14H10F2N2 [ No CAS ]
  • [ 78581-99-4 ]
YieldReaction ConditionsOperation in experiment
97% With triethylsilane; palladium 10% on activated carbon; In tetrahydrofuran; at 20℃; for 18h;Inert atmosphere; General procedure: A 16 mL vial with a PTFE/silicone septum and a nitrogen-bubbler line was charged with N-benzylbenzimidazole (208.1 mg, 1.0 mmol), Pd/C (10 wt %, dry powder, reduced) (20 mg) and THF (5 mL). The mixture was treated at rt with triethylsilane (320 muL, 2.0 mmol) and then stirred under nitrogen for 14 h at rt. The mixture was filtered through a 0.45 muM PTFE syringe filter and the filtrate was concentrated in vacuo. The residue was purified by column chromatography (0 to 10% MeOH/ dichloromethane) to afford benzimidazole as a colorless solid (117.6 mg, 0.996 mmol 99%). The reactions generally exhibit an induction period of 5 to 30 min as indicated by the initiation of gas release (i.e., bubbling) from the reaction mixture. The use of Pd/C on a dry matrix is imperative as wet Pd/C results in decreased yield or no reaction.
  • 34
  • [ 78581-99-4 ]
  • [ 69-72-7 ]
  • 8,9-difluoro-12H-benzo[e]benzo[4,5]imidazo[2,1-b][1,3]oxazine-12-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With pyridine; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper(I) bromide; In para-xylene; at 120℃; for 36h;Schlenk technique; Green chemistry; CuBr 6 mg (0.04 mmol), TEMPO 5 mg (0.03 mmol), compounded in a 25 mL Schlenk reaction tube<strong>[78581-99-4]5,6-difluorobenzimidazole</strong> 62 mg (0.4 mmol),28 mg (0.2 mmol) of salicylic acid (0.2 mmol) and p-xylene (0.5 mL), followed by 33 muL of pyridine (0.4 mmol) were added and the reaction was stirred at 120C for 36 hours under reflux.Cool to room temperature, transfer all to a 25 mL flask, spin off the solvent on a rotary evaporator, add an appropriate amount of silica gel to spin dry, and then use a 300-400 mesh silica gel column. The developing solvent used is petroleum ether:ethyl acetate=16: 1 to 6:1, that is, compound III-9 26mg, yield 48%; white solid
 

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