Structure of 6-Bromo-2-naphthoic acid
CAS No.: 5773-80-8
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CAS No. : | 5773-80-8 |
Formula : | C11H7BrO2 |
M.W : | 251.08 |
SMILES Code : | O=C(O)C1=CC=C2C=C(Br)C=CC2=C1 |
MDL No. : | MFCD01075720 |
Boiling Point : | No data available |
InChI Key : | NPMCAVBMOTZUPD-UHFFFAOYSA-N |
Pubchem ID : | 4549852 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 58.61 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.01 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.97 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.3 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.32 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.0 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.12 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.36 |
Solubility | 0.011 mg/ml ; 0.0000436 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.45 |
Solubility | 0.00882 mg/ml ; 0.0000351 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.3 |
Solubility | 0.0125 mg/ml ; 0.0000497 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
-5.01 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 |
0.56 |
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) |
1.07 |
* 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 |
---|---|---|
93% | With copper(l) iodide; copper(l) chloride In N,N-dimethyl-formamide for 4 h; Inert atmosphere; Reflux | Example 32 Synthesis of Compound 32 6-chloro-2-naphthoic acid A suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCl (11.7 g, 114.64 mmol) and CuI (2.19 g, 11.50 mmol) in degassed DMF (45 mL) was heated to reflux under argon in dark for 4 hrs. After cooling to room temperature, the solution was decanted into H2O (200 mL) and the resulting mixture was extracted with EtOAc (2*500 mL). The combined organic layers were then washed with H2O (4*500 mL) followed by brine (1*500 mL), dried over MgSO4, filtered and concentrated under reduced pressure to dryness. The residue was trituated with CH3CN and the solid obtained was then re-crystallized from EtOAc to give the pure product 32 (2.2 g, 93percent) as an off-white solid. HPLC tR 6.47 min. |
93% | With copper(l) iodide; copper(l) chloride In N,N-dimethyl-formamide for 4 h; Inert atmosphere; Darkness; Reflux | Example 66 - Synthesis of Compound 68 6-chloro-2-naphthoic acid686-chloro-2 -naphthoic acidA suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCI (1 1.7 g, 114.64 mmol) and CuI (2.19 g, 1 1.50 mmol) in degassed DMF (45 ml.) was heated to reflux under argon in dark for 4 hrs. After cooling to room temperature, the solution was decanted into H2O (200 ml.) and the resulting mixture was extracted with EtOAc (2 x 500 mL). The combined organic layers were then washed with H2O (4 x 500 mL) followed by brine (1 x 500 mL), dried over MgSO4, filtered and concentrated under reduced pressure to dryness. The residue was trituated with CH3CN and the solid obtained was then re-crystallized from EtOAc to give the pure product 68 (2.2 g, 93percent) as a off-white solid. HPLC fR 6.47 min. |
93% | With copper(l) iodide; copper(l) chloride In N,N-dimethyl-formamide for 4 h; Reflux; Inert atmosphere; Darkness | A suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCI (1 1.7 g, 114.64 mmol) and CuI (2.19 g, 1 1.50 mmol) in degassed DMF (45 ml.) was heated to reflux under argon in dark for 4 hrs. After cooling to room temperature, the solution was decanted into H2O (200 ml.) and the resulting mixture was extracted with EtOAc (2 x 500 ml_). The combined organic layers were then washed with H2O (4 x 500 ml.) followed by brine (1 x 500 ml_), dried over MgSO4, filtered and concentrated under reduced pressure to dryness. The residue was trituated with CH3CN and the solid obtained was then re-crystallized from EtOAc to give the pure product 70 (2.2 g, 93percent) as a off-white solid. HPLC fe 6.47 min |
93% | With copper(l) iodide; copper(l) chloride In N,N-dimethyl-formamide for 4 h; Inert atmosphere; Darkness; Reflux | A suspension of 6-bromo-2-naphthoic acid (3.0 g, 11.47 mmol), CuCl (11.7 g, 114.64 mmol) and CuI (2.19 g, 11.50 mmol) in degassed DMF (45 mL) was heated to reflux under argon in dark for 4 hrs. After cooling to room temperature, the solution was decanted into H2O (200 mL) and the resulting mixture was extracted with EtOAc (2*500 mL). The combined organic layers were then washed with H2O (4*500 mL) followed by brine (1*500 mL), dried over MgSO4, filtered and concentrated under reduced pressure to dryness. The residue was trituated with CH3CN and the solid obtained was then re-crystallized from EtOAc to give the pure product 68 (2.2 g, 93percent) as a off-white solid. HPLC tR 6.47 min. |
75% | With CuI In N,N-dimethyl-formamide | Step 1. To a solution of 6-bromo-2-naphthoic acid (4.4 g, 17.5 mmol) in 50 mL anhydrous DMF were added CuCl (8.7 g, 87.5 mmol) and CuI (0.2 g). The slurry was refluxed for 1 hour. At room temperature it was diluted with 300 mL EtOAc and stirred for 2 hours. It was filtered through celite. The filtrate was evaporated in vacuuo to afford 6-chloro-2-naphthoic acid (2.7 g, 75percent). ES-MS: (M+H)+207. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Part B. Preparation of 6-bromonaphthalen-2 -amine.; [00748] A solution of the product Part A (5.07g, 20.19mmol) and triethylamine (4.22mL, 3.07g, 30.3mmol) in dry DMF (155mL) was treated with the diphenylphosphoroyl azide (6.55mL, 8.34g, 30.3mmol) followed by stirring at room temperature for 3h. The solution was then treated with water (2OmL) followed by warming at 1000C for Ih. The solution was cooled and the flask fitted with a short- path distillation head and the DMF removed by distillation under high vacuum. The solid residue was dissolved in EtOAc and washed with saturated sodium bicarbonate solution. Filtered through celite and the filtrate was washed with water (3x) and then with brine. Dried over Na2SC^, filtered and concentrated under vacuum to give the title compound as a beige solid (4.48g, 100 percent). | |
100% | [00490] Part B. Preparation of 6-bromonaphthalen-2-amine.; [00491] A solution of the product Part A (5.07g, 20.19mmol) and triethylamine (4.22mL, 3.07g, 30.3mmol) in dry DMF (155mL) was treated with the diphenylphosphoroyl azide (6.55mL, 8.34g, 30.3mmol) followed by stirring at room temperature for 3h. The solution was then treated with water (2OmL) followed by warming at 1000C for Ih. The solution was cooled and the flask fitted with a short- path distillation head and the DMF removed by distillation under high vacuum. The solid residue was dissolved in EtOAc and washed with saturated sodium bicarbonate solution. Filtered through celite and the filtrate was washed with water (3x) and then with brine. Dried over Na2SO4, filtered and concentrated under vacuum to give the title compound as a beige solid (4.48g, 100 percent). | |
100% | Part 1. Preparation of 6-bromonaphthalen-2 -amine.[00328| A solution of the product Part H (5.07 g, 20.19 mmol) and triethylamine (4.22 mL, 3.07 g,30.3 mmol) in dry N.N-dimethylformamide (155mL) was treated with the diphenylphosphoroyl azide(6.55 mL, 8.34 g, 30.3 mmol) followed by stirring at room temperature for 3 hours. The solution was then treated with water (20 mL) followed by warming at 100 0C for 1 hour. The solution was cooled and the flask fitted with a short-path distillation head and the NN-dimethylformamide was removed by distillation under high vacuum. The solid residue was dissolved in ethyl acetate and washed with saturated sodium bicarbonate solution. The organic layer was filtered through diatomaceous earth, and the filtrate was washed with water (3*) and then with brine. The organic layer was dried overNa2SO4, filtered and concentrated under vacuum to give the title compound as a beige solid (4.48 g,100 percent). |
With diphenyl phosphoryl azide; triethylamine; In water; N,N-dimethyl-formamide; at 25 - 100℃; for 5h; | [000705j To a solution of Compound 89A (3.77 g, 15 mmol) and TEA (2.27 g, 22.5 mmol) in DMF (100 mL) was added DPPA (5.47 g, 22.5 mmol). The mixture was stirred at 25 °C for 3 h. Water (30 mL) was added, and the mixture was heated at 100 °C for 2 h. DMF was removed by distillation under vacuum. The residue was dissolved in ethyl acetate (300 mL) and saturated sodium bicarbonate (200 mL), and filtrated through celite. The organic phase was separated, washed with water (200 mL) and brine (200 mL), dried over anhydrous sodium sulfate, and evaporated to furnish Compound 89B. LC-MS (ESI) mlz: 222 [M+H] ?H-NMR (DMSO-d6, 400 MHz) 5 Qpm) 5.55 (s, 2H), 6.83 (s, 1H), 6.99 (d, J= 8.8 Hz, 1H), 7.36 (dd, J= 8.8, 1.6 Hz, 1H), 7.47 (d, J= 8.4 Hz, 1H), 7.59 (d, J= 8.8 Hz, 1H), 7.87 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Reference Example 76-Bromo-2-naphthoic acid (10.1 g, 40.1 mmol) and N,N- dimethylformamide (4.75 g, 65.0 mmol) were added to toluene (80 mL) . To the reaction mixture was added dropwise thionyl chloride (5.7 g, 48.2 mmol) at 45 to 50C, and the mixture was stirred for 1 hr, and allowed to cool to room temperature. The reaction mixture was added dropwise at 10 to 25C to a solution prepared by adding triethylamine (11.4 g, 112.4 mmol) and 40% methylamine methanol solution (8.1 g, 104.4 mmol) to toluene (80 rnL) , and the mixture was stirred at room temperature for 1 hr.. To the reaction mixture was added dropwise water (50 mL) , and the mixture was stirred at room temperature. The crystals were collected by filtration, and washed with a mixed solvent (25 mL) of methanol/water (2:8) to give wet crystals. The total amount of the wet crystals was added to N,N- dimethylacetamide (70 mL) , and dissolved with heating to 60C. The reaction mixture was allowed to cool to room temperature, and water (140 mL) was added dropwise thereto. The crystals were collected by filtration, and washed with water (80 mL) to give wet crystals. The total amount of the wet crystals was suspended in ethyl acetate -(25 mL) with stirring at roomtemperature. The crystals were collected by filtration, and washed with ethyl acetate (5 mL) . The obtained wet crystals were dried under reduced pressure to give 6-bromo-N-methyl-2- naphthamide (9.4 g, 35.6 mmol). yield 89%.¾ NMR (500 MHz, DMSO-d6) delta 2.84 (d, J = 4.4 Hz, 3H) , 7.71 (dd, J = 8.8, 2.2 Hz, 1H) , 7.93 - 8.03 (m, 3H) , 8.28 (d, J = 1.9 Hz, 1H), 8.44 (s, 1H) , 8.62 (d, J = 4.1 Hz, 1H) ; HRMS (ESI) m/z Calcd for a Ci2HuNOBr [M+H]+: 264.0024, Found: 264.0019; Anal. Calcd for a Ci2Hi0NOBr: C, 54.57; H, 3.82; N, 5.30; Br, 30.25. Found: C, 54.56; H, 3.70; N, 5.34; Br, 30.23. | |
82% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; N,N-dimethyl-formamide; at 0 - 20℃; for 18h;Inert atmosphere; | Under an argon atmosphere, to a cooled (0 C) solution of 8 (60.26 g, 240 mmol), EDCI·HCl (55.21 g, 288 mmol), HOBt·H2O (44.1 g, 288 mmol) and N,N-diisopropylethylamine ((i-Pr)2NEt) (37.23 g, 288 mmol) in anhydrous N,N-dimethylformamide (DMF) (960 mL) was added dropwise to a solution of MeNH2 (2 M solution in THF; 192 mL, 384 mmol) and the whole was stirred at room temperature for 18 h. After dilution with water, the precipitate was filtered off, washed with H2O and i-Pr2O and dried under the reduced pressure to give 9a (60.6 g, 82%) as a colorless powder. 1H NMR (CDCl3 + CD3OD) delta: 3.04 (3H, s), 7.60 (1H, dd, J = 1.8 Hz, 8.6 Hz), 7.78 (2H, d, J = 8.6 Hz), 7.85 (1H, dd, J = 1.8 Hz, 8.6 Hz), 8.03 (1H, d, J = 1.8 Hz), 8.25 (1H, s). IR (KBr): 3274, 1638, 1622, 1559, 1495, 1408, 1316, 1159 cm-1. Anal. Calcd for C12H10NOBr.0.1H2O: C, 54.20; H, 3.87; N, 5.27; Br, 30.25. Found: C, 54.03; H, 3.72; N, 5.24. |
80% | 4 Liters of ethyl acetate and 25 ML of DMF were added to 500 g (1.99 mol) of 6-bromo-2-naphthoic acid. 188 ML (2.61 mol, 1.3eq) of thionyl chloride was added dropwise at 30C or lower.. The mixture was stirred at 65C for 30 minutes.. After cooled to 25C, a mixture of 408 ML (3.93 mol, 2eq) of a 40% solution of methylamine in methanol and 558 ML (4.01 mol, 2eq) of triethylamine was added dropwise at 25C or lower.. The mixture was stirred at 25C for 3 hours. 2.5 Liters of water was added dropwise at 25C or lower.. Crystals were filtered, and washed successively with 1.25 liters of a mixed solution of methanol/water=1/4.. Vacuum drying (50C) to a constant weight afforded 422 g of 6-bromo-N-methyl-2-naphthamide (yield 80%).1H NMR (CDCl3+CD3OD): delta 3.04 (3H, s), 7.60 (1H, dd, J=8.6, 1.8 Hz), 7.78 (2H, d, J=8.6 Hz), 7.85 (1H, dd, J=8.6, 1.8 Hz), 8.03 (1H, d, J=1.8 Hz), 8.25 (1H, s). |
Tags: 5773-80-8 synthesis path| 5773-80-8 SDS| 5773-80-8 COA| 5773-80-8 purity| 5773-80-8 application| 5773-80-8 NMR| 5773-80-8 COA| 5773-80-8 structure
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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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