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Structure of 367-31-7

Chemical Structure| 367-31-7

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Product Details of [ 367-31-7 ]

CAS No. :367-31-7
Formula : C6H7FN2
M.W : 126.13
SMILES Code : NC1=CC=C(F)C=C1N
MDL No. :MFCD00042228
InChI Key :KWEWNOOZQVJONF-UHFFFAOYSA-N
Pubchem ID :164584

Safety of [ 367-31-7 ]

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

Computational Chemistry of [ 367-31-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 2.0
Molar Refractivity 35.21
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.

1.0
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

0.75
Log Po/w (WLOGP)?

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

1.43
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.

1.24
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

0.85
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.05

Water Solubility

Log S (ESOL):?

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

-1.59
Solubility 3.26 mg/ml ; 0.0258 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.

-1.42
Solubility 4.77 mg/ml ; 0.0378 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

-1.92
Solubility 1.53 mg/ml ; 0.0121 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

No
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.

-6.54 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 [ 367-31-7 ]

* 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 [ 367-31-7 ]

[ 367-31-7 ] Synthesis Path-Downstream   1~21

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  • [ 1544-75-8 ]
  • 2
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YieldReaction ConditionsOperation in experiment
88% In tetrahydrofuran; at 20℃;Inert atmosphere; Cooling with ice; A stirred solution of 4-fluorobenzene-1 ,2-diamine (15.1 g, 120 mmol) in THF (120 mL) under nitrogen was cooled using an ice-bath and then was treated with di(1 -/-imidazol-1 - yl)methanone (23.4 g, 144 mmol) portion-wise over 15 min. The resulting mixture was slowly warmed to room temperature then was concentrated in vacuo after 2.5 h. The residue was suspended in a mixture of water and DCM (250 mL each) and filtered off. This residue was then washed with water (50 mL) and DCM (50 mL), before being dried at 40 C under vacuum for 16 h to give the title compound (16.0 g, 105 mmol, 88%) as a brown solid. LCMS (high pH): Rt 0.57 min; [M-H+]" = 151.1 deltaEta NMR (400 MHz, DMSO-d6) ppm 10.73 (br s, 1 H), 10.61 (br s, 1 H), 6.91-6.84 (m, 1 H), 6.78-6.70 (m, 2H).
78% In tetrahydrofuran; at 150℃; for 0.333333h;Microwave irradiation; Intermediate 15: 5-Fluoro-1 ,3-dihvdro-2H-benzimidazol-2-one; A mixture of 4-fluoro-1 ,2-diaminobenzene (commercially available, 1.0 g, 7.9 mmol), carbonyldiimidazole (1.4 g) and THF (4 ml) was heated to 150 0C in a microwave reactor and stirred for 10 minutes. The mixture was heated to 150 0C and stirred for a further 10 <n="38"/>minutes. The mixture was cooled to room temperature and concentrated under vacuum. The residue was suspended in dilute hydrochloric acid and filtered. The filter-cake was washed with water and cyclohexane then dried under vacuum to give the title compound as a dark grey solid (0.95 g, 78%). 1 H-NMR (400 MHz, DMSO-d6): delta 10.73 (1 H, br s), 10.62 (1 H, br s), 6.87 (1 H, dd, J 8.5, 5 Hz), 6.78-6.70 (2H, m). UPLC-MS: 0.47 min, m/z 153 [M+H]+.
52% In tetrahydrofuran; at 20℃; a) 4-Fluorobenzene-1,2-diamine (2 g, 15.86 mmol) was dissolved in THF (49.4 ml) and 1,1'-Carbonyldiimidazole (2.83 g, 17.44 mmol) was added at RT. The reaction mixture was stirred overnight at RT. To this was added concentrated ammonia solution (1.5 ml) and the mixture stirred for 30 minutes and then diluted with water (100 ml). The resultant solid was collected by filtration, washed with water, followed by Et2O and then dried in vacuo to afford 5-fluoro-1H-benzo[d]imidazol-2(3H)-one (1.250 g, 52%); 1H NMR (400 MHz, DMSO-d6) 6.66-6.79 (2H, m), 6.81-6.94 (1H, m), 10.64 (1H, s), 10.76 (1H, s); m/z: (ES+) MH+, 151.19.
  • 3
  • [ 3973-08-8 ]
  • [ 367-31-7 ]
  • [ 3575-04-0 ]
  • 4
  • [ 367-31-7 ]
  • [ 2208-07-3 ]
  • [ 118469-15-1 ]
YieldReaction ConditionsOperation in experiment
51% In ethanol; (a) 2-Methyl-5-fluorobenzimidazole Ethyl acetimidate hydrochloride (37.1 g, 0.3 mol) was added to a stirred suspension of 4-fluoro-ortho-phenylenediamine (12.6 g, 0.1 mol) in ethanol (150 ml) at 0 C. The mixture was allowed to warm up to room temperature and stirred overnight. The solvent was removed under reduced pressure and the residue extracted into ethyl acetate (100 ml), washed with water (3*100 ml), dried over anhydrous magnesium sulphate, filtered and evaporated. Crystallisation from ethyl acetate gave 2-methyl-5-fluorobenzimidazole (7.7 g, 51%) as a brown crystalline solid. m.p. 177-178 C. deltaH 7.46 (1H, dd, J 8.8, 4.7 Hz), 7.22 (1H, dd, J 8.9, 2.4 Hz), 6.98 (1H, ddd, J 9.7, 8.9, 2.4 Hz), 2.65 (3H, s).
  • 5
  • [ 6384-92-5 ]
  • [ 367-31-7 ]
  • [ 884047-85-2 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In water;Heating / reflux; Compound 76a:; To a 5.5 N HCI solution (11 mL) of 4-fluoro-1 ,2-phenylene diamine (1.32 g, 10.9 mmol) was added N- methyl-D-aspartic acid (2.00 g, 13.6 mmol). The mixture was refluxed for overnight. It was filtered after cooling down to room temperature. The filtrate was washed with ethyl acetate (10 mL) and EPO <DP n="56"/>concentrated to give the title compound. 1H NMR (CD3OD): delta 7.88 (1 H, dd, J=9.1 , 4.3Hz), 7.65 (1 H, dd, J=8.1 , 2.5Hz), 7.47 (1 H, td, 'J=9.4, 4.3Hz), 4.74 (1 H, dd, J=10.5, 4.5Hz), 4.09 (1 H, dd, J=15.3, 4.4Hz), 3.81 (1H, dd, J=15.2, 10.5Hz), 2.98 (3H, s). LCMS (APCI): 238.1 (M+H+).
  • 6
  • [ 367-31-7 ]
  • [ 123-54-6 ]
  • [ 118469-15-1 ]
YieldReaction ConditionsOperation in experiment
Under an N2 atmosphere, 4-fluorobenzene-l,2-diamine (5.0Og, 39.6 mmol) was suspended in EtOH (220 <n="84"/>mL) and 5M HCl (16OmL) was added. The reaction was warmed to 50C and 2,4- pentandione (8.14mL, 7.93mmol) was added and the reaction was heated to reflux for 30 min. Upon cooling to room temperature, the reaction was neutralized with a saturated solution of NaHCO3(aq) and extracted with dichloromethane. The layers were separated and the aqueous layer was washed with additional dichloromethane (2x). The organics were then combined, dried (Na2SO4), filtered and concentrated in vacuo. The resulting solid was triturated with dichloromethane to afford the title compound. 1H NMR (400MHz) (DMSO-d6) delta 7.43-7.19 (bm, 2H); 6.92 (bs, IH); 2.44 (s, 3H).
  • 8
  • [ 57-55-6 ]
  • [ 367-31-7 ]
  • [ 118469-15-1 ]
  • [ 1977-72-6 ]
  • 9
  • [ 64-17-5 ]
  • [ 367-31-7 ]
  • [ 615-15-6 ]
  • [ 118469-15-1 ]
  • 10
  • [ 53911-68-5 ]
  • [ 367-31-7 ]
  • C17H16ClFN2O3 [ No CAS ]
  • 11
  • [ 124-38-9 ]
  • [ 367-31-7 ]
  • [ 1544-75-8 ]
YieldReaction ConditionsOperation in experiment
87%Chromat. With tetrabutylammonium tungstate; In 1-methyl-pyrrolidin-2-one; at 140℃; under 760.051 Torr; for 24h;Schlenk technique;Catalytic behavior; General procedure: A typical procedure for the I-catalyzed reaction of aryl diamines with 1 atm CO2 was as follows: diamine (1 mmol), I (0.15 mmol), and N-methylpyrrolidone (NMP) (1 mL) were charged in a Schlenk tube with a magnetic stir bar. CO2 (1 atm) was introduced by a balloon, and the reaction mixture was stirred at 140 C for 24 h. The reaction solution was periodically analyzed by GC, LC, GC-MS, or NMR. A Teflon vessel placed in a stainless steel autoclave was used for reactions with CO2 at 20 atm.
  • 13
  • [ 367-31-7 ]
  • 6-fluoro-1H-benzotriazole [ No CAS ]
  • [ 18225-90-6 ]
  • 14
  • [ 1445-45-0 ]
  • [ 367-31-7 ]
  • [ 118469-15-1 ]
YieldReaction ConditionsOperation in experiment
In methanol; at 60℃; for 12.0h; (0618) A mixture of 1,1,1-trimethoxyethane (19.0 g, 159 mmol) and 4-fluorobenzene-1,2-diamine (2.00 g, 15.9 mmol) in MeOH (10 mL) was stirred at 60 C for 12 h. After cooling to ambient temperature, the mixture was concentrated. The residue was purified by flash silica gel chromatography (ISCO; 40 g SepaFlash Silica Flash Column, Eluent of 50100% EA/PE gradient (at) 40 mL/min) to give 5-fluoro-2-methyl-1H-benzo[d]imidazole as a solid.
  • 15
  • [ 1202680-24-7 ]
  • [ 367-31-7 ]
  • [ 1544-75-8 ]
YieldReaction ConditionsOperation in experiment
70% In toluene; for 29h;Reflux; Green chemistry; General procedure: A mixture of 2-phenoxycarbonyl-4,5-dichloropyridazin-3(2H)-one (2a, 1.2 equiv), compounds 4 (1 equiv), and toluene (10 mL)was stirred at reflux conditions until amide intermediate wasconsumed (monitored by TLC). After cooling to r.t., the resultingprecipitate was filtered off and the solvent was evaporatedunder reduced pressure. The residue was transferred to anopen-bed silica gel column (3 × 7 cm). The column was elutedwith n-hexane-THF (1:2, v/v). Fractions containing compounds5 were combined and evaporated under reduced pressure togive compounds 5.
  • 16
  • [ 367-31-7 ]
  • [ 90176-80-0 ]
  • 5-fluoro-2-(4-fluoro-2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% In ethanol; at 80℃; for 4h; General procedure: ZrO2-Al2O3 solid acid catalytic material was added to the stirred solution of O-phenylenediamines and different substituted aromatic aldehydes in a suitable solvent, and the resulting mixture was heated at a particular temperature and monitored by TLC. After the completion of the reaction, the reaction mixture was cooled and filtered and the residue was washed with ethanol to recover the solid acid catalyst. Filtrate was evaporated in vacuum to get the crude reaction product, which was then purified by silica-gel column chromatography using a suitable mobile phase to separate the desired product. The reaction products were characterized by melting point, 1H NMR and 13C NMR spectroscopy (Bruker, 400 MHz), LC-MS (Varian), and HPLC (Waters) techniques
  • 17
  • [ 367-31-7 ]
  • [ 64-19-7 ]
  • [ 118469-15-1 ]
  • 18
  • [ 367-31-7 ]
  • [ 503-38-8 ]
  • [ 1544-75-8 ]
YieldReaction ConditionsOperation in experiment
93% With triethylamine; In dichloromethane; at 0 - 20℃; for 2h; [0278] To a solution of 4-fluorobenzene-1,2-diamine lb (1.39 g, 11.0 mmol) and triethylamine (3.26 mE, 23.2 mmol) in methylene chloride (20 mE) was added dropwise a solution of diphosgene (0.69 mE, 5.72 mmol) in methylene chloride (5 mE) at 0 to 5 C. The resulting suspension was stirred for 2 hours at room temperature and filtered. The collected white solid was washed with water and dried to give compound 2b (1.56 g, 93%). ?H NMR (400 MHz, DMSO-d5) oe 10.73 (s, 1H), 10.61 (s, 1H), 6.97-6.81 (m, 1H), 6.74 (m, 2H); MS (ESI): mlz 153.1 [M+1]
  • 19
  • [ 141-82-2 ]
  • [ 367-31-7 ]
  • [ 118469-15-1 ]
  • 20
  • [ 5417-17-4 ]
  • [ 367-31-7 ]
  • 2-(2'-chloro-3',4'-dimethoxyphenyl)-5-fluoro-1H-benzo[d]imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
62.3% With sodium metabisulfite; In N,N-dimethyl-formamide; for 4h;Reflux; General procedure: o-Phenylene diamine derivative (1 mmol) and substitutedbenzaldehyde (1 mmol) were taken in N,N-dimethylformamide(10 mL) into a round-bottomed flask 100 mL. A pinch of sodiummetabisulfite (Na2S2O5) was added into it and refluxed solution for4 h. Progress of reactionwas checked by thin layer chromatography(TLC). After completion, reaction mixture was poured onto crushedice (100 mL). Precipitates were appeared immediately which werefiltered. The obtained solid crude products were crystallized fromethanol. Compounds were structurally characterized by variousspectroscopic techniques.
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