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Structure of 1897-52-5
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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.
4.5
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Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
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Search for reports by entering the product batch number.
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CAS No. : | 1897-52-5 |
Formula : | C7H3F2N |
M.W : | 139.10 |
SMILES Code : | N#CC1=C(F)C=CC=C1F |
MDL No. : | MFCD00001778 |
InChI Key : | BNBRIFIJRKJGEI-UHFFFAOYSA-N |
Pubchem ID : | 74695 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H301+H311+H331-H315-H319 |
Precautionary Statements: | P501-P261-P270-P271-P264-P280-P337+P313-P305+P351+P338-P361+P364-P332+P313-P301+P310+P330-P302+P352+P312-P304+P340+P311-P403+P233-P405 |
Class: | 6.1 |
UN#: | 3439 |
Packing Group: | Ⅲ |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 31.07 |
TPSA ? Topological Polar Surface Area: Calculated from |
23.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.61 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.84 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.68 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.32 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.64 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.22 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.31 |
Solubility | 0.688 mg/ml ; 0.00495 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.96 |
Solubility | 1.52 mg/ml ; 0.011 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.01 |
Solubility | 0.135 mg/ml ; 0.000971 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) |
Yes |
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 |
-5.84 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 |
2.0 |
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 |
0.0 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) |
1.41 |
* 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 |
---|---|---|
71% | at 35℃; Inert atmosphere | 2 L four-necked flask, 600mL60percent sulfuric acid was added, with stirring was added 2,6-difluorobenzonitrile 139.0g (1.0mol), in N2Under protection, control of the reaction temperature below 35°C, points added 250.5g of KBrO3 10 portions(1.5mol), TLC monitoring, the reaction 5-6 days, until starting material disappeared point, the reaction was stopped, the ice preparation 800mL20percent saline solution, the reaction mixture was poured into iced brine.After settlement products, quickly suction filtration to give a crude orange product with CCl4The crude product was dissolved, respectively, with 5percent NaHSO3Solution, saturated Na2CO3Solution was washed with water until the solution was neutral, dried over anhydrous sodium sulfate, the solution was filtered, 60 water bath rotary evaporation to give a pale yellow liquid was cooled to a standstill for some time as a pale yellow solid, distillation under reduced pressure, condensed steam heated, oil bath was raised to 90 deg.] C, taking the temperature of 58-62°C steam fraction, and cooled to obtain a white solid product, 71percent yield. |
71% | at 35℃; Inert atmosphere | Take 2 L four bottles, add 600 mL of 60percent sulfuric acid, electric stirring by adding 2,6_ difluorobenzonitrile 139.0 g (1.0 mol). Under N2 protection, the control reaction temperature was below 35 ° C, and 250 μm g of KBr03 (1.5 mol) was added to 10 batches. TLC monitoring, reaction 5-6 days, until the raw material point disappears, stop the reaction, the preparation of 800 mL 20percent ice salt solution, the reaction solution Into the ice salt. After the product settling, the rapid filtration, the orange crude products, with CC14 dissolved crude products, respectively, with 5percent Of NaHS03 solution, saturated Na2C03 solution and water to the solution was neutral, dried over anhydrous sodium sulfate, the solution was filtered, the water bath 60 ° C steamed to obtain light yellow liquid, rest for some time to cool into a pale yellow solid, vacuum distillation, warm water condensing steam, oil The bath was heated to 90 ° C and the fraction at a steam temperature of 58-62 ° C was cooled to give a white solid product in 71percent yield |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | at 0 - 20℃; for 24 h; | A solution of 2,6- difluorobenzonitrile (5.0 g, 36 mmol) in concentrated sulfuric acid (25 mL) was treated with NBS (7.0 g, 29.5 mmol) at 0 °C and stirred at ambient temperature for 24 hours. Ice (about 100 g) was added to the reaction mixture. After melting, the mixture was extracted with MTBE (100 mL). The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with 5: 1 to 1 :2 hexanes/ethyl acetate to give both 3- bromo-2,6-difluorobenzonitrile (5.5 g, 70percent yield) as solid and 3-bromo-2,6- difluorobenzamide (2.1 g, 25percent) as solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In methanol; at 0 - 20℃; | Synthesis Route 21.5: 2-Fluoro-6-methoxybenzonitrile (analogous to WO 99/14187):640.5 g (4.6 mol) of difluorobenzonitrile were dissolved in 3.5 I of methanol and then cooled to 0-50C. 828.8 g of 30% strength sodium methoxide solution were added dropwise in this temperature range, and the reaction mixture was stirred at room temperature overnight. Then the reaction mixture was added to 20 I of water and the precipitate was filtered off with suction and washed twice with water and twice with heptane. The solid was dried in vacuo at 50C. Yield: 740 g (99% of theory) of a white solid with a purity of >95% according to GC.1H NMR (in CDCI3): delta = 3.95 ppm (s, 3H, 0-CH3), 6.85 ppm (m, 2H, arom. H), 7.5 ppm (q, 1H, arom. H). ; |
In methanol; at 0 - 20℃; | I. Synthesis Examples; Example 1.1 : 2-Difluoromethoxy-6-prop-2-ynylsulfamoyl-thiobenzamide (4); 1.1. 2-Fluoro-6-methoxybenzonitrile:; 640.5 g (4.6 mol) of difluorobenzonitrile have been dissolved in 3.5 I of methanol and then cooled to 0-5 C. 828.8 g of 30% strength sodium methoxide solution have been added dropwise in this temperature range, and the reaction mixture has been stirred at room temperature overnight. Then the reaction mixture has been added to 20 I of water and the precipitate has been filtered off with suction and washed twice with water and twice with heptane. The solid has been dried in vacuo at 50 C to yield 740 g (455 mmol) of the title compound as a white solid. | |
In methanol; at 20℃; | To a solution of A6.1 (500 g, 3.6 mol) in 2.5 L MeOH was added sodium methoxide (388 g, 7.2 mol) in portions slowly. The mixture was stirred at rt overnight. The reaction mixture was poured into 15 L H2O and the precipitate was filtered off and washed twice with 2.0 L H2O to give the title compound (1140 g) as a white solid, the crude product will be used in next step without further purification. 1H NMR (500 MHz, CDCl3) delta ppm 3.96 (s, 3H), 6.79 (dd, 2H), 7.52 (dd, 1H) |
In methanol; at 20℃;Large scale; | To a solution of A3.l (500 g, 3.6 mol) in 2.5 L MeOH was added sodium methoxide (388 g, 7.2 mol) in portions slowly. The mixture was stirred at rt overnight. The reaction mixture was poured into 15 L H20 andthe precipitate was filtered off and washed twice with 2.0 L H20 to give the title compound (1140 g) as a white solid, the crude product will be used in next step without further purification. 1H NMR (500 MHz, CDCI3) O ppm 3.96 (5, 3H), 6.79 (dd, 2H), 7.52 (dd, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32.5% | With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 5h; | 2,6-Difluorobenzonitrile (5.89 g), <strong>[6494-19-5]3-methyl-6-nitroindazole</strong> (5.00 g) and powdered potassium carbonate (11.7 g) were stirred in DMF (85 mL) in an atmosphere of nitrogen at 90°C for 5 hours. The reaction mixture was cooled to room temperature, and a precipitated insoluble substance was removed by filtration. The DMF was distilled away from the resulting filtrate under reduced pressure. The resulting residue was dissolved in ethyl acetate, water was added to the solution, and then the mixture was separated. The organic layer was sequentially washed with water and a saturated brine solution and was dried over anhydrous magnesium sulfate. The ethyl acetate was distilled away under reduced pressure. Subsequently, the resulting residue was purified by silica gel column chromatography (eluate: ethyl acetate/hexane = 40/60) to give Compound 3 (2.72 g, yield 32.5percent) as crystals. Melting point: 199.7°C 1H-NMR (300 MHz, CDCl3) delta (ppm): 8.41 (1H, d, J = 2.0 Hz), 8.16 (1H, dd, J = 2.0, 8.8 Hz), 7.89 (1H, d, J = 8.8 Hz), 7.81 (1H, dt, J = 6.0, 8.3 Hz), 7.51 (1H, d, J = 8.3 Hz), 7.35 (1H, dt, J = 0.9, 8.3 Hz), and 2.73 (3H, s). 13C-NMR (75 MHz, CDCl3) delta(ppm): 164.5 (d, 1J = 262 Hz), 147.7, 146.5, 141.8 (d, 3J = 2.5 Hz), 139.1, 135.3 (d, 3J = 10.0 Hz), 128.4, 121.9, 121.1 (d, 4J = 3.8 Hz), 116.9, 115.6 (d, 2J = 19.9 Hz), 111.2, 106.6, 99.3 (d, 2J = 17.4 Hz), and 12.0. IR (KBr, cm-1): 2,233 (CN), 1,535 and 1,350 (NO2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Example 94; 5-[1-(2-Trifluoromethylphenyl)-ethoxy]-quinazoline-2,4-diamine; [00287] Step 1; A solution of alpha-methyl-2- (trifluoromethyl)benzyl (750 mg; 3.9 mmol) in dimethylformamide was added to a cooled (0 C) slurry of sodium hydride (156 mg; 3.9 mmol) in dimethylformamide under nitrogen atmosphere. The reaction mixture was slowly warmed to room temperature, and stirred for 45 minutes. In another vessel, a solution of 2,6-difluorobenzonitrile (543 mg, 3.9 mmol) in dimethylfomamide was chilled to 0 C, and activiated anion was added over 20 minutes. Mixture was then stirred 2 hours at room temperature. The reaction mixture was poured on crushed ice-water, stirred, filtered, washed with water and dried to afford 1.2 g of solid (99% yield) of 2-fluoro-6-[1-(2-trifluoromethylphenyl)-ethoxy]- benzonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 78; 5-[1-(3,4-Dichlorophenyl)-ethoxy]-quinazoline-2,4-diamine; [00244] Step 1; To a cold (ice water) suspension of sodium hydride (316 mg; 7.9 mmol) in anhydrous DMF (10 mL) is added a solution of 1-(3,4-dichlorophenyl)- ethanol (1.40 g; 7.3 mmol) in anhydrous DMF (5 mL) over 30 minutes. After allowing to room temperature over 30 minutes, this solution is added to a cold (ice water) stirred solution of 2,6-difluorobenzonitrile (1.0 g; 7.2 mmol) in anhydrous DMF (15 mL), and allowed to room temperature over 2 hours. The reaction mixture is poured into ice water with vigorous stirring and extracted with ethyl acetate. The organics are separated and dried over magnesium sulfate. The solvent is removed and the resulting oil is dried under vacuum at 30 C overnight to give 1.93 gm of 2-[1- (3,4-dichlorophenyl) -ethoxy]-6-fluorobenzonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 20; 5-(1-Methylpiperidin-3-ylmethoxy)quinazoline-2,4-diamine; [0093] Step 1; Sodium hydride (60percent; 316 mg; 7.9 mmol) was suspended in DMF and cooled to 0 °C. 1-Methylpiperdin-3-ylmethanol (998 mg; 7.5 mmol) was added dropwise to the sodium hydride mixture. The solution was allowed to warm to room temperature and stirred for 30 minutes. The solution was then cooled to 0 °C. 2,6- Difluorobenzonitrile (1.1 g; 7.9 mmol) in DMF was cooled to 0° C and the alcohol mixture was added dropwise to the benzonitrile solution and allowed to warm to room temperature overnight. The solution was poured into water and extracted with dichloromethane and solvent removed. Purification by column chromatography (10percent ethyl acetate/ hexane) to yield 79 milligrams of 2-fluoro-6-(1-methylpiperidin-3- ylmethoxy) benzonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: Example 1 Preparation of Compound Yhhu-0967 (5-methoxy-2,4-diaminoquinazoline) [0029] 2.53 g (79.08 mmol) of methanol was dropped into 5.18 g (86.27 mmol) of 40% sodium hydride suspension in tetrahydrofuran (150 ml) at 0 C. and stirred for 10 min, followed by dropwise addition of 10.0 g (71.89 mmol) of 2,6-difluorobenzonitrile in tetrahydrofuran (100 ml). The reaction mixture as stirred at room temperature for 10 h to complete the reaction. 200 ml of water was added thereto to destroy the excess sodium hydride, and the reaction mixture was extracted with 500 ml of ethyl acetate. The organic layer was dried with anhydrous sodium sulfate and evaporated to dryness. The residue was passed through column chromatography to provide an intermediate. The intermediate and 17.41 g (143.78 mmol) of guanidine carbonate were heated to 140 C. in 300 ml of N,N-dimethylacetamide and stirred for 8 h to complete the reaction. The reaction mixture was evaporated to dryness, then diluted with 200 ml of water and extracted with 400 ml of dichloromethane. The organic layer was dried with anhydrous sodium sulfate and then evaporated to dryness. The residue was passed through column chromatography to proved 9.85 g of compound Yhhu-0967 with a total yield of 72% in the two steps). [0030] 1H NMR (300 MHz, CHLOROFORM-d) d ppm 3.97 (s, 3H) 4.83 (br. s., 2H) 5.68 (br. s., 1H) 6.53 (d, J=8.06 Hz, 1H) 7.03 (d, J=8.55 Hz, 1H) 7.45 (t, J=8.18 Hz, 2H) |
Tags: 1897-52-5 synthesis path| 1897-52-5 SDS| 1897-52-5 COA| 1897-52-5 purity| 1897-52-5 application| 1897-52-5 NMR| 1897-52-5 COA| 1897-52-5 structure
A383887 [1803792-98-4]
2,6-Difluoro-4-methylbenzonitrile
Similarity: 0.98
A101003 [1003712-20-6]
2,5-Difluoro-3-methylbenzonitrile
Similarity: 0.93
A138431 [867367-02-0]
4-Fluoro-3,5-dimethylbenzonitrile
Similarity: 0.92
A383887 [1803792-98-4]
2,6-Difluoro-4-methylbenzonitrile
Similarity: 0.98
A101003 [1003712-20-6]
2,5-Difluoro-3-methylbenzonitrile
Similarity: 0.93
A138431 [867367-02-0]
4-Fluoro-3,5-dimethylbenzonitrile
Similarity: 0.92
A383887 [1803792-98-4]
2,6-Difluoro-4-methylbenzonitrile
Similarity: 0.98
A101003 [1003712-20-6]
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Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
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Code | Phrase |
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P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
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P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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