Structure of 169045-04-9
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CAS No. : | 169045-04-9 |
Formula : | C8H8BrNO3 |
M.W : | 246.06 |
SMILES Code : | O=C(O)C1=CC(Br)=C(OC)C=C1N |
MDL No. : | MFCD21868786 |
InChI Key : | YTAASTFSTXYEIX-UHFFFAOYSA-N |
Pubchem ID : | 19701926 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 52.0 |
TPSA ? Topological Polar Surface Area: Calculated from | 72.55 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.52 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 1.98 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 1.75 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 0.37 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 1.19 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 1.36 |
Log S (ESOL):? ESOL: Topological method implemented from | -2.82 |
Solubility | 0.37 mg/ml ; 0.0015 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -3.13 |
Solubility | 0.183 mg/ml ; 0.000742 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -2.4 |
Solubility | 0.984 mg/ml ; 0.004 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 | -6.4 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 | 1.0 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) | 1.55 |
* 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% | In ethanol; for 24.0h;Heating / reflux; | 6-bromo-7-methoxyquinazoline-4(3H)-one <strong>[169045-04-9]2-amino-5-bromo-4-methoxybenzoic acid</strong> (type T) (5.63 g, 23 mmol) was dissolved in EtOH (100 mL), formamidine acetate (4.76 g, 46 mmol) added and refluxed for 1 d. Water (200 mL) was then added, the precipitated product filtered out and washed with 70% ethanol. (Yield: 4.14 g, 71%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0 - 20℃; for 1.0h; | To a solution of 2-amino-4-methoxybenzoic acid (4.00 g, 23.93 mmol) in DMF (120 mL) at 0 C was added NBS (4.68 g, 26.3 mmol). The cooling bath was removedand the reaction mixture was warmed up to room temperature and was stirred at room temperature for 1 h. The mixture was cooled to 0 C and was treated with saturated sodium sulfite solution (25 mL) and was stirred for 5 mm. The pH of the mixture was adjusted to pH = 3 using conc. HC1 (ca. 10-15 mL was added). The reaction mixture was transferred to a separatory funnel containing water (100 mL). Theaqueous layer was extracted with ether (1 x 250 mL then 4 x 100 mL). The combined organic layers were washed with water (3 x 50 mL), brine (50 mL), dried over MgSO4, filtered, and concentrated to afford 2-amino-5-bromo-4- methoxybenzoic acid (5.90 g, 100% yield) as a solid: ?H NMR (400 MHz, DMSOd6) oe 7.78 (s, 1H), 6.43 (s, 1H), 3.81 (s, 3H), 2.90 (s, 1H), 2.74 (s, 1H); MS (ESI) m/e228.0 [(M+H-H2O), calcd for C8H7BrNO2 228.0]. |
77% | With bromine; acetic acid; at 20 - 40℃; for 18.0h; | 2-amino-5-bromo-4-methoxybenzoic acid 2-amino-4-methoxybenzoic acid (5 g, 30 mmol) was suspended in acetic acid (100 mL) and bromine (0.57 mL, 11.25 mmol) added at RT. The mixture was stirred approx. 15 h at RT, then additional bromine (0.2 mL, 3.75 mmol) was added and the reaction mixture held at 40 C. for 3 hours. The reaction course was tracked by thin-film chromatography, the product filtered out and washed with a little water. (Yield: 5.63 g, 77%) |
With bromine; In acetic acid; at 0 - 20℃; for 8.0h; | Step 1: 2-Amino-5-bromo-4-methoxybenzoic acidTo a stirred suspension of 2-amino-4-methoxybenzoic acid (5 g, 0.029 mol) in acetic acid (100 mL) was added bromine (1.23 mL, 0.023 mol) dropwise at 0C. The reaction mixture was stirred at room temperature for 8 h. The separated solid was filtered, washed with water (30 mL) and dried under vacuum to afford the product as white solid (6.3 g, 86 %). As per the LC-MS data this solid contains 14% of starting material, 22% of dibromo byproduct and 61% of desired compound.1H NMR (400 MHz, DMSO-de) : delta 7.76 (s, 1H), 6.42 (s, 1H), 3.72 (s, 3H); ESI-MS: Calculated mass: 244.97; Observed mass LC-MS: 246.0 [M + H]+RT: 2.07 min. |
1.3 g | With N-Bromosuccinimide; In dichloromethane; N,N-dimethyl-formamide; at 0 - 20℃; for 4.0h; | To a mixture of 4-methoxyanthranilic acid (0.67 g, 4.0 mmol) in DCM (10 mL) and DMF (3 mL) was added NBS (0.71 g, 4.0 mmol) at 0 C. The mixture was stirred at room temperature for 4 h, then concentrated and subjected to silica gel chromatography (5-100% EtOAc/Heptane) to provide 2-amino-5-bromo-4-methoxybenzoic acid as a beige solid (1 .30 g, containing 1 equivalent succinamide). MS (M-1 ) = 244.3/246.3. 1H NMR (DMSO-d6) delta 7.76 (s, 1 H), 6.42 (s, 1 H), 3.79 (s, 3H). This material was used without further purification. |
With bromine; acetic acid; In acetonitrile; at 0 - 20℃; for 1.0h;Inert atmosphere; | 2-Amino-4-methoxybenzoic acid (5.00 g, 29.91 mmol) was dissolved in acetic acid (10 mL) and acetonitrile (100 mL), slowly added dropwise with liquid bromine (4.78 g, 29.91 mmol) at 0 C and under nitrogen protection,, and stirred at 20 C for 1 hour. TLC showed that the reaction was complete. After the reaction solution was concentrated, water (100 ml) and petroleum ether (100 ml) were successively used for making a slurry, which was vaccum dried to obtain compound 1A. 1H NMR (400MHz, DMSO-d6) delta= 7.76 (s, 1H), 6.41 (s, 1H), 3.79 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With piperidine; In methanol; for 1.0h;Heating / reflux; | 6-Bromo-7-methoxy-3H-quinazolin-4-one 2-Amino-5-bromo-4-methoxybenzoic acid (1.56 g, 6.34 mmol) is dissolved in methanol (15 ml), treated with piperidine (0.063 ml, 0.63 mmol) and 1,3,5-triazine (772 mg, 9.5 mmol) and refluxed for one hour. After cooling to room temperature, the resulting crystals are filtered off with suction and washed with methanol. The desired product is obtained in 63% yield (1.01 g). 1H-NMR (300 MHz, DMSO-d6): delta 3.95 (s, 3H), 7.20 (s, 1H), 8.08 (s, 1H), 8.16 (s, 1H), 12.2 (br, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5.5 g | With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 1.0h; | Step 2: Methyl 2-amino-5-bromo-4-methoxybenzoateTo a stirred suspension of <strong>[169045-04-9]2-amino-5-bromo-4-methoxybenzoic acid</strong> (6.3 g, 0.025 mol) and potassium carbonate (7.06 g, 0.051 mol) in N,ll-dimethyl formamide (63 mL) was added methyl iodide (5.45 g, 0.038 mol) dropwise at 0C. After the addition was complete, the reaction mixture was stirred at room temperature for 1 h. The mixture was poured into ice cold water (500 mL) and extracted with ethyl acetate (2 x 200 mL). The combined organic layers were washed with water (100 mL) followed by brine solution, dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated under reduced pressure and the crude product was purified using column chromatography (100-200 mesh silica gel, 20% EtOAc in hexane) to afford the title compound as white solid (5.5 g, 83% yield). *H NMR (400 MHz, DMSO-d6) : delta 7.78 (s, 1H), 6.85 (brs, 2H), 6.44 (s, 1H), 3.80 (s, 3H), 3.75 (s, 3H). ESI-MS: Calculated mass: 258.98; Observed mass: 258.3 [M-H] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.858 g | In ethanol; for 24.0h;Reflux; | A mixture of <strong>[169045-04-9]2-amino-5-bromo-4-methoxybenzoic acid</strong> (1 .25 g, 3.6 mmol) and formimidamide acetate (0.75 g, 7.2 mmol) in EtOH (15 mL) was refluxed for 24 h. The mixture was cooled to room temperature and the solid was filtered, washed with water, and dried to provide 6- bromo-7-methoxyquinazolin-4(1 H)-one as a white solid (0.858 g). MS (M+1 ) = 255.0/257.0. 1H NMR (DMSO-d6) delta 12.30 (br. s, 1 H), 8.21 (s, 1 H), 8.12 (s, 1 H), 7.25 (s, 1 H), 4.00 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 1.0h; | EDC (5.42 g, 28.3 mmol) was added to a solution of 2-amino-5-bromo-4- methoxybenzoic acid (5.80 g, 23.57 mmol) in CH2C12 (120 mL). HOBT hydrate (4.33 g, 28.3 mmol) was added and the reaction mixture was stirred for 1 h at room temperature. The reaction mixture was quenched with 30% ammonium hydroxidesolution (58 mL) and stirring was continued for an additional 1 h. The reaction mixture was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (150 mL). The aqueous layer was extracted with CH2C12 containing 5% MeOH (3 x 150 mL). The combined organic layers were washed with brine (150 mL), dried over MgSO4, filtered, and concentrated to give 2-amino-5-bromo-4-methoxybenzamide (5.04 g, 87% yield) as a colorless solid: ?H NMR (400 MHz, DMSO-d6) oe 7.79 (s, 1H), 6.92 (s, 2H), 6.38 (s, 1H), 3.78 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Nitromethane (0.63 ml, 11.7 mmol) was added dropwise at room temperature to a solution of sodium hydroxide (14.7 g, 368 mmol) in water (33 ml) with stirring. The mixture was subsequently warmed slowly at 45 C. for 5 minutes with stirring. The reaction solution was then cooled to room temperature, and nitromethane (0.63 ml, 11.7 mmol) was again added dropwise. The reaction mixture was subsequently stirred for a further 10 minutes, during which a clear, reddish solution formed. After brief warming (5 minutes) at 50 C., the mixture was cooled to room temperature and decanted off onto ice (11 g). The aqueous solution was carefully acidified to pH<2 using conc. hydrochloric acid and subsequently immediately added to a solution of <strong>[169045-04-9]2-amino-5-bromo-4-methoxybenzoic acid</strong> (8.00 g, 32.5 mmol) in water (259 ml), acidified using conc. hydrochloric acid (126 ml, 2.75 mol), with stirring. The suspension obtained was stirred overnight and subsequently filtered. The residue was dried at 50, giving 9.60 g (93%) of 5-bromo-4-methoxy-2-[[(e)-2-nitrovinyl]amino]benzoic acid as colourless solid. |
Tags: 169045-04-9 synthesis path| 169045-04-9 SDS| 169045-04-9 COA| 169045-04-9 purity| 169045-04-9 application| 169045-04-9 NMR| 169045-04-9 COA| 169045-04-9 structure
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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 |
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