Structure of 367-31-7
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
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 |
52.04 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.75 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.43 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.24 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.85 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.05 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.59 |
Solubility | 3.26 mg/ml ; 0.0258 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.42 |
Solubility | 4.77 mg/ml ; 0.0378 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.92 |
Solubility | 1.53 mg/ml ; 0.0121 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.54 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.0 |
* 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.
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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+). |
Yield | Reaction Conditions | Operation 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). |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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 |
Yield | Reaction Conditions | Operation 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] |
Yield | Reaction Conditions | Operation 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. |
A1003675 [55495-99-3]
4-Fluorobenzene-1,2-diamine hydrochloride
Reason: Free-salt
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