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CAS No. : | 345-24-4 |
Formula : | C6H2BrF2NO2 |
M.W : | 237.99 |
SMILES Code : | FC1=C(Br)C=C([N+]([O-])=O)C(F)=C1 |
MDL No. : | MFCD00129166 |
InChI Key : | OOUUWURPSUSDTD-UHFFFAOYSA-N |
Pubchem ID : | 223078 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 42.88 |
TPSA ? Topological Polar Surface Area: Calculated from | 45.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.54 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 2.64 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 3.48 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 2.49 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 1.26 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 2.28 |
Log S (ESOL):? ESOL: Topological method implemented from | -3.28 |
Solubility | 0.124 mg/ml ; 0.000522 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -3.25 |
Solubility | 0.133 mg/ml ; 0.000559 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -3.19 |
Solubility | 0.152 mg/ml ; 0.000638 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 | -5.88 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 | 0.0 |
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 | 3.0 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) | 2.17 |
* 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 |
---|---|---|
90% | With iron; acetic acid; In ethanol; at 80℃; for 2h; | To a stirred solution of 1-bromo-2,4-difluoro-5-nitro-benzene (1) (3.0 g, 0.013 mol) in ethanol (40 mL), iron powder (4.928 g, 0.088 mol) and acetic acid (10.60 mL, 0.176 mol) were added and the reaction mixture was stirred at 80 C. for 2 h. The progress of the reaction was monitored by TLC. The reaction mixture was filtered through a celite bed and the filtrate was concentrated under reduced pressure. The residue was dissolved in water and extracted with ethyl acetate. Combined organic layers were concentrated under reduced pressure to afford the title compound as an off white solid. Yield (2.0 g, 90%). LCMS (ESI positive ion) m/z: calculated: 208.1; observed: 210.1 (M+2). |
68.21% | With iron; ammonium chloride; In ethanol; water; for 6h; | 5-Bromo-2,4-difluoronitrobenzene (2.36 g, 10 mmol) was dissolved in a mixed solvent of ethanol / water (5/1, 24 mL), and iron powder (1.68 g, 30 mmol) and ammonium chloride ( 1.60g, 30mmol), stir evenly, heat up the reaction after dripping, TLC monitor, the raw materials are completely reacted after 6h, suction filtration under mild heat conditions after stopping the reaction, the filtrate is selected (PE / EA = 10/1), the column is shallow Yellow oil 1.73 g, yield: 68.21%. |
59.1% | With water; iron; ammonium chloride; In tetrahydrofuran; ethanol; at 95℃; for 1.5h;Heating / reflux; | A 250-mL RB-flask, charged with 5-bromo-2,4-difluoronitrobenzene (5.04 g, 21.3 [MMOL),] saturated [NH4CL] (25.0 mL), iron powder (5.00 g, 89.5 mmol), ethanol (100 mL), THF (50.0 mL) and water (25.0 mL) was refluxed at [95 C] for 1.5 hours. After cooling to room temperature, saturated [NAHCO3] (100 mL) was added and the mixture was filtered through Celite and the Celite was washed with EtOAc (3 x 50 mL). The combined filtrates were washed with H20 and brine, dried over [MGSO4,] filtered and concentrated in vacuo. The crude product was purified by flash chromatography (EtOAc: hexanes 1: 9) to afford 5- bromor-2, [4-DIFLUOROANILINE] (2.61 g, [59. 1%). 1H] NMR (400 MHz, [CDC13)] 5 6.97 (dd, 1H, J = 7.2, 6.7 Hz), 6.85 (t, 1H, [J] = 8.2 Hz), 3.63 (br, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | In methanol; at 0 - 20℃; for 22.0h; | To a stirred solution of l-bromo-2,4-difluoro-5-nitro-benzene (12.1 g, 50.8 mmol) in MeOH (100 mL) was added 25% sodium methoxide in MeOH (12 mL, 53.4 mmol, 12 mL) at 0 C, and the reaction mixture was stirred at 0C for 2h and then at RT for 20h. Volatile solvent was removed under reduced pressure, and the resultant residue was partitioned between 'PrOAc and water. The organic layer was washed with water and brine, dried over Na2S04. filtered and concentrated in vacuo. The crude product was purified by column chromatography (SiCh:?PrOAc / heptane) to afford 10.9g (86% yield) of a mixture of l-bromo-4-fluoro-2- methoxy-5-nitro-benzene and l-bromo-2-fluoro-4-methoxy-5-nitro-benzene (~2: l ratio). 1- Bromo-4-fluoro-2-methoxy-5-nitrobenzene: ' H NMR (400 MHz, CDCf) d 8.36 (d, J = 8.0 Hz, 1H), 6.77 (d, J = 12.3 Hz, 1H), 4.00 (s, 3H); l-bromo-2-fluoro-4-methoxy-5-nitro-benzene: 'H NMR (400 MHz, CDCf) d 8.16 (d, J = 7.1 Hz, 1H), 6.89 (d, J = 9.8 Hz, 1H), 3.97 (s, 3H); |
In methanol; at 0℃; for 2.0h; | Example 4el-Bromo-2-fluoro-4-methoxy-5-nitro-benzene (10c) and l-Bromo-4-fluoro-2- methoxy-5-nitro-benzene l-Bromo-2,4-difluoro-5-nitro-benzene (960mg, 4.0 mmol) was dissolved in MeOH (20 mL) was cooled to 0C and treated with 0.5M Sodium Methoxide in MeOH solution (8.1 mL, 4 mmol). After 2 hours the reaction solution was concentrated under reduced pressure and the residue was partitioned between EtOAc and water. The organic phase was dried over sodium sulfate (Na2S04), filtered, and concentrated under reduced pressure to give 833mg (83%) of yellowish oil. 1H NMR spectral analysis supported that the product was a mixture of l-Bromo-2-fluoro-4-methoxy-5-nitro-benzene and l-Bromo-4- fluoro-2-methoxy-5-nitro-benzene (~1 :2 ratio). The assignments of the respective regioisomers were determined based on further analysis of a purified l-Bromo-2-fluoro-4- methoxy-5-nitro-benzene analog, generated from the subsequent steps to this reaction. 1H NMR (DMSO- 6) delta 8.41-8.39 (d, 0.63H), 8.36-8.34 (d, 0.26H), 7.57-7.54 (d, 0.30H), 7.45-7.42 (d, 0.70H), 4.01 (s, 2.2H), 3.95 (s, 0.9H). | |
In methanol; at 0 - 20℃; for 18.0h;Reflux; | At 0 C., sodium methoxide (344 mg, 6.3 mmol) in dry MeOH (7 mL) was added dropwise to 1-bromo-2,4-dif- luoro-5-nitrobenzene(1 g, 4.2 mmol) in dry MeOH (l8mL). The mixture was stirred at room temperature for 10 hand then refluxed for 8 h. After extractive work up, purification by silica gel chromatography (PE:EA=1:0 to 10:1) gave a mix-ture of the two title compounds (765 mg, 72.9%) in about a 2:1 ratio as a yellow solid. LCMS: 249.9 (M+H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
c) 6-Bromo-5-fluoroindolin-2-one A suspension of (4-bromo-5-fluoro-2-nitrophenyl)-acetic acid/ (2-bromo-5-fluoro-4-nitro- phenyl)-acetic acid (2.6: 1 mixture, 37.3 g, 134 mmol) and iron (30.0 g, 537 mmol) in acetic acid (671 ml) was heated to 100C for 7 hours and then cooled to room temperature. Remaining elemental iron was removed with a magnetic rod. Ice water (900 ml) was added to the reaction mixture. The precipitate was filtered off, washed four times with water and then suspended in an ice-cold aqueous solution of 25% HC1 (300 ml) and cone. HC1 (50 ml). After stirring for 10 minutes the precipitate was filtered off and washed four times with water. The precipitate was suspended in a mixture of 1 M aqueous Na2C03 (400 ml) solution and 0.1 M NaOH (100 ml) and stirred for 40 minutes. The precipitate was filtered off and washed four times with 0.1 M aqueous NaOH, three times with water and once with diisopropylether to give title compound as light grey solid (20.5 g). MS ESI (m/z): 228.0/ 230.0 [(M-H)"]. 1H NMR (DMSO-D6, 400 MHz): (ppm) = 10.47 (bs, 1H), 7.31-7.28 (m, 1H), 7.01-6.99 (m, 1H), 3.49 (s, 2H). | ||
20.5 g | a) 2-(4-Bromo-5-fluoro-2-nitro-phenyl)-malonic acid dimethyl ester/ 2-(2-Bromo-5-fluoro-4-nitro-phenyl)-malonic acid dimethyl ester A suspension of NaH (60 % in mineral oil, 20.2 g, 504 mmol) in dioxane (233 ml) was cooled to11 C. A solution of 1-bromo-2,4-difluoro-5-nitrobenzene (50 g, 26.5 ml, 210 mmol) anddimethyl malonate (33.3 g, 28.9 ml, 242 mmol) in dioxane (467 ml) was carefully added at 11 - 14 C within 45 minutes (gas evolution). After completion of the addition the reaction mixture was kept at 12 C for another hour and then warmed to room temperature. After 16 hours the reaction mixture was cooled to 10 C and 100 ml saturated aqueous ammonium chloride solutionwas added. The reaction mixture was diluted with tert-butyl methyl ether, water and saturated aqueous ammonium chloride solution. The aqueous phase was extracted with tert-butyl methyl ether, the combined organic phases were washed with saturated aqueous ammonium chloride solution and brine and dried over sodium sulfate. The solvent was evaporated and the residue purified by silica gel chromatography using ethyl acetate heptane as eluent. The title compoundswere obtained as yellow liquid (53.7 g) as a 2.6:1 mixture and used for the next reaction without further purification.. A mixture of 2-(4-bromo-5 -fluoro-2-nitro-phenyl)-malonic acid dimethyl ester 2-(2-bromo-5- fluoro-4-nitro-phenyl)-malonic acid dimethyl ester (2.6:1 mixture, 53.7 g, 153 mmol) and 6 Maqueous hydrochloric acid (767 ml) was heated to reflux for 7 hours and then cooled to 5 C. The precipitate was filtered, washed with water and with n-pentane and then coevaporated 3 times with toluene to give 25.9 g of a mixture of the title compounds as white solid. The mother liquor was extracted with ethyl acetate and the combined organic phases dried over sodium sulfate. The solvent was evaporated and the residue triturated with n-pentane and then coevaporated with toluene to give 11.42 g of a mixture of the title compounds as an off-white solid. This material was combined with the first crop to give a total of 37.32 g of the title compounds as a 2.6 :1 mixture which was used for the next reaction without further purification.A suspension of (4-bromo-5-fluoro-2-nitrophenyl)-acetic acid/ (2-bromo-5-fluoro-4-nitro- phenyl)-acetic acid (2.6:1 mixture, 37.3 g, 134 mmol) and iron (30.0 g, 537 mmol) in acetic acid (671 ml) was heated to 100 C for 7 hours and then cooled to room temperature. Remaining elemental iron was removed with a magnetic rod. Ice water (900 ml) was added to the reaction mixture. The precipitate was filtered off, washed four times with water and then suspended in anice-cold aqueous solution of 25 % HC1 (300 ml) and conc. HC1 (50 ml). After stuffing for 10 minutes the precipitate was filtered off and washed four times with water.The precipitate was suspended in a mixture of 1 M aqueous Na2CO3 (400 ml) solution and 0.1 M NaOH (100 ml) and stirred for 40 minutes. The precipitate was filtered off and washed four times with 0.1 M aqueous NaOH, three times with water and once with diisopropylether to givetitle compound as light grey solid (20.5 g). MS ESI (m/z): 228.0/ 230.0 [(M-H)i.1H NMR (DMSO-D6, 400 MHz): (ppm) = 10.47 (bs, 1H), 7.3 1-7.28 (m, 1H), 7.01-6.99 (m, 1H), 3.49 (s, 2H). |
Tags: 345-24-4 synthesis path| 345-24-4 SDS| 345-24-4 COA| 345-24-4 purity| 345-24-4 application| 345-24-4 NMR| 345-24-4 COA| 345-24-4 structure
A117497 [741721-51-7]
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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 |
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The concentration of the dissolution solution you need to prepare is mg/mL