Structure of 1544-75-8
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CAS No. : | 1544-75-8 |
Formula : | C7H5FN2O |
M.W : | 152.13 |
SMILES Code : | O=C1NC2=CC=C(F)C=C2N1 |
MDL No. : | MFCD05663528 |
InChI Key : | DZRTZDURJKZGSP-UHFFFAOYSA-N |
Pubchem ID : | 10329453 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 38.88 |
TPSA ? Topological Polar Surface Area: Calculated from | 48.65 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.2 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 1.22 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 1.42 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 1.27 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 2.59 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 1.54 |
Log S (ESOL):? ESOL: Topological method implemented from | -2.16 |
Solubility | 1.06 mg/ml ; 0.00696 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -1.84 |
Solubility | 2.2 mg/ml ; 0.0145 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -3.08 |
Solubility | 0.127 mg/ml ; 0.000832 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 | -6.36 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 | 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) | 1.75 |
* 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 |
---|---|---|
83% | With sodium hydrogen sulfide; In 1-methyl-pyrrolidin-2-one; at 90℃; under 22502.3 Torr; for 24h; | General procedure: Add in a 15ml Teflon-lined reactor216 mg (2 mmol) of o-phenylenediamine, 56 mg (1 mmol)NaHS (molar ratio of o-phenylenediamine to NaHS is 1:2),Add 1 mL of NMP as the reaction solvent.Put the magnets and tighten the reactor.Then charge 3MPa of carbon dioxide,The reaction was stirred at 90 C for 24 hours.After cooling the reactor to room temperature,Extracted with ethyl acetate,Washed with saturated saline,After drying the organic layer, the solvent is removed under reduced pressure to give a crude material;The crude product is separated by recrystallization or column chromatography (200-300 mesh silica gel,Petroleum ether and ethyl acetate as eluent)99% white powder benzimidazolone 116mg,The yield was 88%. |
(4) 3-(2-(benzoxazyl))-6-fluorobenzimidazol-2-(1H)-one; (Compound 14); mp: 295-296 C. | ||
(10) 3-(2-(7-fluorobenzoxazyl))-5-fluorobenzimidazol-2-(1H)-one; (Compound 18); mp: 268-270 C. |
(5) 3-(2-(6-fluorobenzoxazyl))-6-fluorobenzimidazol-2-(1H)-one; (Compound: 4); mp 284-285 C. | ||
(9) 3-(2-(7-fluorobenzoxazyl))-6-fluorobenzimidazol-2-(1H)-one; (Compound 3); mp: 284-285 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | b) A solution of <strong>[1544-75-8]5-fluoro-1H-benzo[d]imidazol-2(3H)-one</strong> (1.25 g, 8.22 mmol) in phosphorus oxychloride (25.2 ml, 270.34 mmol) was heated for 18 hours at 100 C. The reaction mixture was cooled to RT and excess of POCl3 was evaporated in vacuo. The residue was neutralized with saturated NaHCO3 solution (10 ml) and extracted with EtOAc (3×20 ml). The organic phase was washed with brine and then dried over MgSO4, filtered and concentrated under reduced pressure to afford 2-chloro-6-fluoro-1H-benzo[d]imidazole (1.146 g, 82%); 1H NMR (400 MHz, DMSO-d6) 7.09 (1H, ddd), 7.36 (1H, dd), 7.53 (1H, dd); m/z: (ES+) MH+, 171.34. |
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 |
---|---|---|
88% | With trichlorophosphate; at 100℃; for 18h; | 10279] A solution of 5-fluoro- 1 ,3-dihydro-2H-benzo[d] imidazol-2-one 2b (1.562 g, 10.3 mmol) in phosphorus oxychloride (14 mE, 154.5 mmol) was heated for 18 hours at 100 C. The reaction mixture was cooled to room temperature and excess of P0C13 was evaporated in vacuo. The residue was neutralized with saturated NaHCO3 solution (10 mE) and extracted with EtOAc (3x20 mE). The organic phase was washed with brine and then dried over Mg504, filtered, and concentrated under reduced pressure to afford 2-chloro-6-fluoro-l H-benzo[d]imidazole 3b (1.552 g, 88%). ?H NMR (400 MHz, DMSO-d5) oe 7.51 (s, 1H), 7.34 (d, J=7.6 Hz, 1H), 7.08 (m, 1H); MS (ESI): mlz 171.0 [M+l] |
Intermediate 14: 2-Chloro-5-fluoro-1 H-benzimidazole; A mixture of 5-fluoro-1 ,3-dihydro-2H-benzimidazol-2-one (Intermediate 15, 0.75 g, 4.1 mmol) and phosphorus oxychloride (2.1 ml) was heated to 110 0C and stirred for 5 hours.The mixture was cooled to room temperature and quenched by addition of ice. The mixture was left to stand 30 minutes, then basified to pH 9 with aqueous ammonium hydroxide solution. The resulting precipitate was filtered off, washed with water and dried under vacuum. The residue was dissolved in ethyl acetate, and filtered. The filtrate was concentrated under vacuum to give the title compound (0.49 g). 1 H-NMR (400 MHz,DMSO-d6): delta 7.52 (1 H, dd, J 9, 5 Hz), 7.35 (1 H, dd, J 9, 2.5 Hz) and 7.08 (1 H, ddd, J 10,9, 2.5 Hz). UPLC-MS: 0.55 min, m/z 171 [M+H]+.(Alternatively, 5-fluoro-2-chloro-1 H-benzimidazole is commercially available) |
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 |
---|---|---|
91% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16h; | [00312] lodomethane (0.82 mL, 13.15 mmol) was added to a mixture of <strong>[1544-75-8]5-fluoro-1,3-dihydro-2H-benzimidazol-2-one</strong> (500. mg, 3.29 mmol) and potassium carbonate (1.81 g, 13.15mmol) in DMF (25 mL), and the reaction mixture stirred at ambient temperature for 16 h. DCM(30 mL) and water (60 mL) were added and the mixture stirred for 5 min. The DCM layer wasisolated by passing through a hydrophobic frit and the aqueous washed with DCM (2 x 50mL). The combined DCM extracts were concentrated under reduced pressure to yield 5-fluoro-1,3-dimethyl-benzimidazol-2-one (556 mg, 2.99 mmol, 91%).[00313] 1H NMR (300MHz, CDCI3) 5 = 6.91 - 6.71 (m, 3H), 3.42 (s, 3H), 3.41 (s, 3H) |
81% | A solution of 5-fluoro-1 H-benzo[d]imidazol-2(3H)-one (16.0 g, 105 mmol) in DMF (400 mL) under nitrogen was cooled with an ice-bath, using a mechanical stirrer for agitation. It was then treated over 10 min with sodium hydride (60% w/w in mineral oil, 13.1 g, 327 mmol) and the resulting mixture was stirred at this temperature for 30 min before being treated with iodomethane (26.3 mL, 422 mmol) over 30 min. The resulting mixture was then allowed to warm to room temperature and after 1 h was carefully treated with water (500 mL). The aqueous phase was extracted with EtOAc (3 x 800 mL) and the combined organics were washed with brine (1 L), dried over MgS04 and concentrated in vacuo. Purification of the brown residue by flash chromatography on silica gel (SP4, 1.5 kg column, gradient: 0 to 25% (3: 1 EtOAc/EtOH) in cyclohexane) gave the title compound (15.4 g, 86 mmol, 81 %) as a pink solid. LCMS (high pH): Rt 0.76 min; [M+H+]+ = 181.1 deltaEta NMR (400 MHz, CDCI3) ppm 6.86-6.76 (m, 2H), 6.71 (dd, J = 8.3, 2.3 Hz, 1 H), 3.39 (s, 3H), 3.38 (s, 3H). |
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 |
---|---|---|
50% | With trimethylsilylazide; In tetrahydrofuran; for 30h;Reflux; | General procedure: To a solution of phthalic anhydride in THF (1.0 mm), TMSA (4.0 equiv.) was added and the mixture was refluxed with stirring for 30 h. The resulting solution was concentrated in vacuo until a solid formed. The solid was washed with diethyl ether (5×4 ml) to obtain high purity imidazolin-2-ones 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.1% | In ethanol; at 20℃; for 15h; | Obtained through a method the N- acetyl benzylamine piperazine (II) intermediate (19. 6mmol), an alcoholic solution of formaldehyde (16. 3mmol), 5- fluoro-1,3-dihydro-benzimidazol-2-one (16. 3mmol) into 30ml of absolute ethanol, at room temperature for 15h. The reaction was concentrated under reduced pressure to give a crude oil. The crude product was purified by silica gel column chromatography to obtain the free base of N- benzyl-2- {4 - [(5-fluoro-2-oxo-2,3-dihydro-benzo -111- [(1] imidazol-1 yl) methyl] piperazin-1-yl} acetamide (V_19), 4.67g, yield 72.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
370 mg | With caesium carbonate; In acetone; at 65℃; for 6h;Sealed tube; | Step 1. A mixture of 5-fluoro-lH-benzo[d]imidazol-2(3H)-one (200 mg, 1.26 mmol), cesium carbonate (905 mg, 2.78 mmol) and tert-butyl 2-bromoacetate (0.39 mL, 2.65 mmol) in acetone (10 mL) was sealed and heated in an oil bath at 65 C for 6 h. The reaction mixture was filtered and concentrated in vacuo, and the residual oil taken up into DCM (5 mL) and purified by FCC (40 g silica gel, eluted with gradient 10-50% EtOAc-Hexanes) to afford di-tert-butyl 2,2'-(5-fluoro2-oxo-lH-benzo[d]imidazole-l,3(2H)-diyl)diacetate (370 mg) as a white solid. LC-MS retention time = 1.31 min; m/z = 269.2 [M-2(t- Bu)+H]+. (Column: Waters Aquity BEH C18 2.1 X 50 mm 1.7^m-particles; Solvent A = 100% Water/ 0.05% TFA; Solvent B = 100% Acetonitrile/0.05% TFA; Flow Rate = 0.8 mL/min. Start % B = 2; Final % B = 98; Gradient Time = 1.5 minutes; Wavelength = 220 nm). |
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] |
Tags: 1544-75-8 synthesis path| 1544-75-8 SDS| 1544-75-8 COA| 1544-75-8 purity| 1544-75-8 application| 1544-75-8 NMR| 1544-75-8 COA| 1544-75-8 structure
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P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
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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