Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 76179-40-3 | MDL No. : | MFCD00061131 |
Formula : | C6H6F2N2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | PPWRHKISAQTCCG-UHFFFAOYSA-N |
M.W : | 144.12 | Pubchem ID : | 2736755 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 35.17 |
TPSA : | 52.04 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.64 cm/s |
Log Po/w (iLOGP) : | 1.09 |
Log Po/w (XLOGP3) : | 0.76 |
Log Po/w (WLOGP) : | 1.99 |
Log Po/w (MLOGP) : | 1.68 |
Log Po/w (SILICOS-IT) : | 1.26 |
Consensus Log Po/w : | 1.36 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.66 |
Solubility : | 3.18 mg/ml ; 0.0221 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.43 |
Solubility : | 5.32 mg/ml ; 0.0369 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -2.21 |
Solubility : | 0.881 mg/ml ; 0.00611 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.08 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
98% | With hydrogen In methanol for 3 h; | 4,5-Difluoro-2-nitro-aniline (10 g, 57 mmol) and 10percent palladium on carbon (2.0 g, 1.9 mmol) were placed in methanol (150 mL). The mixture was hydrogenated at 50 psi in a hydrogenator. After 3 hours the reaction mixture was filtered through diatomaceous earth and concentrated to a solid which was dried overnight (8.05 g, 98percent). |
97% | With palladium on activated charcoal; hydrogen In methanol at 20℃; for 12 h; | Step 1: A mixture of 4,5-difluoro-2-nitroaniline (1.73 g, 10 mmol), palladium on activated charcoal (200 mg),and MeOH (50 mL) was stirred under hydrogen (1 atm) at rt for 12 h. The mixture was filtered to remove the catalystand the filtrate was concentrated under reduced pressure to afford 4,5-difluorobenzene-1,2-diamine (1.42 g, 97percent) as abrown solid, which was not purified further. 1H NMR (300 MHz, CDCl3) δ 6.50 (m, 2H), 2.75 - 3.48 (br s, 4H). |
62% | With tin(ll) chloride In ethanol at 20℃; for 0.5 h; Heating / reflux | A mixture of 4,5-difluoro-2- nitro-phenylamine (10.00 g, 57.46 mmol) and tin(II) chloride dihydrate (64.83 g, 287.32 mmol) in ethanol (100 mL) was heated to reflux under nitrogen atmosphere for 30 min. After mixture was cooled down to room temperature, the pH of the solution was made basic (10 to 12) by addition of 5percent of sodium hydroxide solution. The solution was extracted with ethyl acetate. The combined organic layer was dried over magnesium sulfate. Solvent was removed under reduced pressure and the residue was crystallized in hexane to give a white solid (6.05 g, 62percent). 1H NMR (300 MHz, CDC13): 6 6.53 (t, J= 8.5 Hz, 2H), 3.38 (br, 4H). HRMS: Calcd. For C6H6F2N2 144.0499, Found 144.0500. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With hydrogenchloride In methanol | 4,5-Difluoro-1,2-phenylenediamine (10) To a solution of 5.55 g (31.876 mmole) of 4,5-difluoro-2-nitroaniline in 50 mL of MeOH, were added 100 mL of 2 N HCl and 8.90 g (159.380 mmole) of iron powder. The reaction mixture was stirred at room temperature for 2 hr and then filtered. The filtrate was neutralized with conc. NH4 OH to ~pH 8. The resulting suspension was filtered again and the filter cake was washed thoroughly with MeOH. The filtrate and washings were combined, concentrated to ~100 mL, and extracted with CHCl3 (100 mL*3). The CHCl3 solution was washed with a sat. NaCl solution (100 mL*2), dried (Na2 SO4), and evaporated. The residue was coevaporated with CHCl3 to give 3.515 g (77percent) of 10. This material was used in the next reaction without further purification. A brown crystalline sample of 10 was obtained by recrystallization from CCl4. 1 H NMR (DMSO-d6): d6.44 (t, 2,3-H and 6-H, JF-H =10.5 H), 4.59 (br. s, 4,2*NH2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | at 80℃; for 12 h; | A solution of 4,5-difluorobenzene-1 ,2-diamine (1.5 g, 10 mmol) in formic acid (20 mL) was heated at 80°C for 12 hours. The reaction mixture was cooled to 25°C 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, 88percent). MS (ESI) m/z: 155 [M+H]+. |
75% | at 100℃; for 1 h; | 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 5percentMeOH in DCM to afford 5,6-difluoro-1H-benzo[d]imidazole as (1.12 g, 75percent) as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.07 (s, 1H), 7.44 (m, 2H); LCMS (ESI) m/z 155 (M + H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | at 120℃; for 12 h; | 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). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74.2% | With iodine In ethanol at 0℃; | Example 54; N-Cyclohexyl-2-[5,6-difluoro-2-(methoxy-phenyl-methyl)-benzoimidazol-1-yl]-2-(4-methoxy-phenyl)-acetamide; Step 1; (2-Amino-4,5-difluoro-phenyl)-carbamic acid tert-butyl ester [CAS RN 1000698-88-3] (for alternative preparation see also Example 1, Step 1); To a ice-bath cooled mixture of 1,2-diamino-4,5-difluorobenzene (10.00 g, 69 mmol, 1.0 equiv., [CAS RN 76179-40-3]) and di-tert-butyl-dicarbonate (12.87 g, 59 mmol, 0.85 equiv; [CAS RN 24424-99-5]) in absolute ethanol (150 mL) was added iodine (0.18 g, 0.007 mmol, 0.01 equiv; [CAS RN 7553-56-2]). The mixture was maintained overnight in the refrigerator. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography on silica gel (500 g, 1:0-->19:1 dichloromethane/ethyl acetate eluant) to afford, in order of elution, the bis-boc derivative as an orange solid (1.58 g, 6.6percent), and the desired compound as a white solid (12.58 g, 74.2percent). |
74% | With iodine In ethanolCooling with ice | To a cooled (ice-bath) mixture of l,2-diamino-4,5-difluorobenzene (10.00 g, 69 mmol, 1.0 equiv., [CAS RN 76179-40-3]) and di-tert-butyl-dicarbonate (12.87 g, 59 mmol, 0.85 equiv; [CAS RN 24424-99-5]) in absolute ethanol (150ml) was added iodine (0.18g, 0.007 mmol, 0.01 equiv. [CAS RN 7553-56-2]). The mixture was maintained overnight in the refrigerator. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography on silica gel (50Og, 1:0 to 19:1 CH2Cl2/AcOEt eluant) to afford, in order of elution, the bis-boc derivative as an orange solid (1.58 g, 6 percent), and the desired compound as a white solid (12.58g, 740Zo)11H NMR (300 MHz, DMSO): <5 1.46 ( s, 9H), 5.03 (br s, 2H), 6.65 (dd, / = 8.2 Hz, / = 12.9 Hz, IH), 7.30 (dd, / = 8.9 Hz, / = 12.3 Hz, IH), 8.38 (br s, IH). MS (ISN): 243.4 [M-H]". |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With thionyl chloride; triethylamine In chloroformReflux; Inert atmosphere | To a 500 mL two- necked round bottom flask were added 4,5-difluorobenzene-l,2-diamine (10.0 g, 0.070 mol, Matrix Scientific), anhydrous CHC13 (250 mL) and anhydrous triethylamine (40 mL, 0.28 mol). The solution was stirred until the diamine was completely dissolved. Thionyl chloride (SOCI2, 10.5 mL, 0.145 mol) was added dropwise using an addition funnel and the mixture heated to reflux for 5 h. The mixture was then cooled to room temperature, poured into 500 mL of distilled H20, and then extracted with CH2C1 (100 mLx3). The collected organic layers were combined and dried over MgS04. The solvent was removed in vacuo and the resulting crude product purified by column chromatography using hexane/ethyl acetate (1 :4) as eluent. After removal of solvent the product was obtained as brownish-white crystalline solid. Recovered yield: 10.65 g (90percent). 1H NMR (600MHz, CDC13): δ 7.73 (t, 2H, JF.H = 12.0 Hz, 12.0 Hz). |
53% | With thionyl chloride; triethylamine In dichloromethane at 0℃; for 1 h; Inert atmosphere; Reflux | A dry 1000 mL round bottom flask, equipped with a condenser, was purged with nitrogen and charged with 4,5-difluorobenzene-1,2-diamine (10 g, 0.069 mol), 400 mL of anhydrous methylene chloride (CH2Cl2), and triethylamine (38.7 mL, 0.28 mol). The reaction flask was cooled to 0° C. and thionyl chloride (30.2 mL, 0.41 mol) was added drop-wise. The ice bath was removed and the mixture was heated to reflux for 1 hour. Completion of reaction was monitored by GC-MS. As the reaction was completed, the mixture was concentrated down, quenched with cold water, and extracted with CH2Cl2 (3×300 mL). The organic phase was dried over anhydrous MgSO4, filtered, and concentrated down. The final product was purified using column chromatography on silica gel with hexanes/ethyl acetate (80:20) gradient to yield white crystalline solid (6.3 g, 53percent). Spectral data: 1H NMR (300 MHz, CDCl3): δH 7.75 (t, 2H). |
10.5 g | at 0 - 25℃; for 6 h; | Into a 500 ml flask were charged 10.2 g (70.8 mmol) of 4,5-difluoro-1,2-diaminobenzene (compound 21) (manufactured by Tokyo Chemical Industry Co., Ltd.) and 150 mL of pyridine and a uniform solution was obtained. The flask was cooled down to 0° C., and 16.0 g (134 mmol) of thionyl chloride was dropped into the flask. After dropping, the flask was warmed at 25° C., and the solution was reacted for 6 hours. Thereafter, 250 ml of water was added to the reaction liquid, and further, chloroform was added and an organic layer containing the reaction product was extracted. The organic layer as a chloroform solution was dried over sodium sulfate, and filtrated. The filtrate was concentrated by an evaporator, and the deposited solid was purified by recrystallization. As the solvent for recrystallization, methanol was used. After purification, 10.5 g (61.0 mmol) of a compound 22 was obtained. 1H-NMR (CDCl3, δ (ppm)): 7.75 (s, 2H); 19F-NMR (CDCl3, δ (ppm)): −128.3 (s, 2F) |
10.5 g | at 0 - 25℃; for 6 h; | 500ml flask was added 10.2g (70.8mmol) 4,5- difluoro-1,2-diaminobenzene (Tokyo Chemical Industry Co., Ltd.),150mL of pyridine, to form a uniform solution. The flask was kept at 0 , the thionyl chloride 16.0g (134mmol) in the flask. After the dropwise addition, the flask was heated to 25 , the reaction for 6 hours. Then, the reaction mixture was added water 250ml, and then chloroform was added, the organic layer containing the reaction product was extracted. The chloroform solution was dried over sodium sulfate, concentrated by evaporation and the precipitated solid was purified by recrystallization use. Recrystallization using methanol solvent. After purification, to give 10.5g (61.0mmol) compound 8. |
10.5 g | at 0 - 25℃; for 6 h; | A 500ml flaskPut in4,5-difluoro-1,2-diaminobenzene (Tokyo Chemical Industry Co., Ltd.) 10.2g (70.8mmol), pyridine 150mL, homogeneous solution. In the case of the flask was maintained at 0 , theDropped into the flaskChlorinating thionyl chloride 16.0g (134mmol).After the dropwise addition, the flask was heated to 25 , a reaction for 6 hours. Then, water was added 250ml, reaction product with chloroform extraction. With a chloroform solution of sodium sulfate as the organic layer was dried, filtered. Using a rotary evaporator and the filtrate was concentrated by recrystallization of the precipitated solid was purified. Solvents for recrystallization using methanol. After purification, the compound obtained 10.5g of 26 (61.0mmol). |
10.5 g | at 0 - 25℃; for 6 h; | A 500 ml flask was charged with 10.2 g (70.8 mmol) of 4,5-difluoro-1,2-diaminobenzene (compound 1) (manufactured by Tokyo Chemical Industry Co., Ltd.) 150 mL of pyridine was added to make a homogeneous solution. The flask was cooled to 0 ° C., To the flask, 16.0 g (134 mmol) of thionyl chloride was added dropwise. After the dropwise addition, the flask was warmed to 25 ° C. and the reaction was carried out for 6 hours. Thereafter, 250 ml of water was added to the reaction solution, and further chloroform was added to extract the organic layer containing the reaction product. The organic layer which is a chloroform solution was dried over sodium sulfate and filtered. The filtrate was concentrated with an evaporator, and the precipitated solid was purified by recrystallization. Methanol was used as a solvent for recrystallization. After purification, 10.5 g (61.0 mmol) of Compound 2 was obtained |
10.5 g | at 0 - 25℃; for 6 h; | 10.2 g (70.8 mmol) of 4,5-difluoro-1,2-diaminobenzene (Compound 1) (manufactured by Tokyo Chemical Industry Co., Ltd.) and 150 mL of pyridine were placed in a 500 ml flask, did. The flask was cooled to 0 ° C., and 16.0 g (134 mmol) of thionyl chloride was added dropwise into the flask. After the dropwise addition, the flask was warmed to 25 ° C. and the reaction was carried out for 6 hours. Thereafter, 250 ml of water was added to the reaction solution, and chloroform was further added to extract the organic layer containing the reaction product. The organic layer which is a chloroform solution was dried over sodium sulfate and filtered. The filtrate was concentrated with an evaporator, and the precipitated solid was purified by recrystallization. Methanol was used as a solvent for recrystallization. After purification, 10.5 g (61.0 mmol) of Compound 2 was obtained |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With thionyl chloride; triethylamine In ethyl acetate | Example 1 Synthesis of 5,6-difluorobenzo[c][1,2,5]thiadiazole A dry 1000 mL round bottom flask, equipped with a condenser, was purged with nitrogen and charged with 4,5-difluorobenzene-1,2-diamine (10 g, 0.069 mol), 400 mL of anhydrous methylene chloride (CH2Cl2), and triethylamine (38.7 mL, 0.28 mol). The reaction flask was cooled to 0° C. and thionyl chloride (30.2 mL, 0.41 mol) was added drop-wise. The ice bath was removed and the mixture was heated to reflux for 1 hour. Completion of reaction was monitored by GC-MS. As the reaction was completed, the mixture was concentrated down, quenched with cold water, and extracted with CH2Cl2 (3*300 mL). The organic phase was dried over anhydrous MgSO4, filtered, and concentrated down. The final product was purified using column chromatography on silica gel with hexanes/ethyl acetate (80:20) gradient to yield white crystalline solid (6.3 g, 53percent). Spectral data: 1H NMR (300 MHz, CDCl3): δH 7.75 (t, 2H). |