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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.
Synonyms: Tetraphthalaldehydic acid
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CAS No. : | 619-66-9 |
Formula : | C8H6O3 |
M.W : | 150.13 |
SMILES Code : | C1=C(C=CC(=C1)C=O)C(O)=O |
Synonyms : |
Tetraphthalaldehydic acid
|
MDL No. : | MFCD00006951 |
InChI Key : | GOUHYARYYWKXHS-UHFFFAOYSA-N |
Pubchem ID : | 12088 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
With 1,1'-carbonyldiimidazole; In tetrahydrofuran; water; | EXAMPLE 6 p-Formyl-N,N-dimethylbenzamide benzylamidinohydrazone hydrochloride A mixture of 15.0 g. of 4-carboxybenzaldehyde, 17.0 g. of N,N'-carbonyldiimidazole and 150 ml. of tetrahydrofuran is allowed to stand at room temperature for one hour. Dimethylamine is passed thru the above solution for one hour and the reaction mixture is allowed to stand at room temperature for 18 hours, then is heated at reflux temperature for one hour. Water is added and the solvent is distilled off. The residue is extracted with methylenechloride. The organic layer is washed with dilute hydrochloric acid and water, dried over magnesium sulfate and concentrated to an oil. The oil is triturated with a little methylene chloride and the insoluble material is filtered off. The mother liquor is concentrated and 7.9 g. of p-formyl-N,N-dimethylbenzamide is obtained as an oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 278 4-[(2-Methoxy-5-phenylcarbamoyl-phenylamino)-methyl]-benzoic acid The title compound has been made using the procedure of Example 50, but using <strong>[120-35-4]3-amino-4-methoxy-benzanilide</strong> and 4carboxybenzaldehyde, which are available from Aldrich, as starting materials; mp >240 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With ammonium acetate; glacial acetic acid; for 4h;Reflux; Inert atmosphere; | A mixture of ammonium acetate (3.5g, 45mmol), 4-carboxybenzaldehyde (150mg, 1mmol) 1,10-phenanthroline-5,6-dione (210mg, 1mmol) and glacial acetic acid (40mL) was refluxed for 4h under argon atmosphere. After cooled to room temperature, diluted with amount of water (30mL) and neutralized with concentrated aqueous ammonia. The resulting orange solution was removed to give an orange powder, which was washed with amounts of water and dried under vacuum. Yield: 255mg, 75%. MALDI-TOF-MS (DMSO, m/z): 341.1 ([M+1]+). |
67.1% | With ammonium acetate; glacial acetic acid; at 110℃; for 4h; | General procedure: A solution containing 1,10-phenanthroline-5,6-dione (1.6 mmol, 347 mg), substituted benzaldehyde (1.6 mmol), 20 ml of HAc and NH4Ac (33 mmol, 2.53 g), was heated at 110 C under reflux for 4 h. Then, 20 ml of water was added and the pH value was adjusted to 7.0 at room temperature. The solution was filtered and dried in vacuum to obtain a yellow precipitate. The product was purified in a silica gel column by using ethanol as eluent. 1a: yield 78.4%; mp. 217-219 C, ESI-MS (in MeOH): m/z: 219.1, ([M + H]), 438.1,([M + 2H]2+). 2a: yield 79.5%; mp. 226-228 C, ESI-MS (in MeOH): m/z: 339.15, ([M + H]+), 678.1, ([M + 2H]2+). 3a: yield 64.4%; mp. 262-265 C, ESI-MS (in MeOH): m/z: 325.1, ([M + H]+), 650.3, ([M + 2H]2+). 4a: yield 75.7%; mp. 234-236 C, ESI-MS (in MeOH): m/z: 311.1, ([M + H]+). 5a: yield 67.1%; mp. 232-235 C, ESI-MS (in MeOH): m/z: 339.1, ([M + H]+). 6a: yield 67.7%; mp. 280-283 C, ESI-MS (in MeOH): m/z: 363.1, ([M + H]+), 726.1, ([M + 2H]2+). 7a: yield 63.4%; mp. 269-273 C, ESI-MS (in MeOH): m/z: 375.2, ([M + H]+), 750, ([M 2H]2+), 772.8, ([M + H + Na]2+). |
63% | With ammonium acetate; glacial acetic acid; for 2h;Reflux; | General procedure: o-TFPIP was prepared by a similar method to that reported [31], and with some modification. In general,a solution of 1,10-phenanthraquinone (525 mg, 2.5 mmol), ammonium acetate (3.88 g, 50 mmol), and2-trifluoridphenylaldehyde (609 mg, 3.5 mmol) in 10 mL of glacial acetic acid was refluxed for 2 h. The cooled deep red solution was diluted with 25 mL of water and neutralized with ammonium hydroxide.Then the mixture was filtered and the precipitates washed with water and acetone, then dried andpurified by chromatography over 60-80 mesh SiO2 using absolute ethanol as eluent. The obtained yield was 516 mg (54%) [32]. |
With ammonium acetate; glacial acetic acid; at 100℃; for 0.333333h;Microwave irradiation; | General procedure: Phenanthroimidazole derivatives were synthesized in accordancewith the literature procedure with some modifications. Generally, amixture of 1,10-phenanthroline-5,6-dione (1.50 mmol), benzaldehyde(2.25 mmol), ammonium acetate (51.9 mmol), and glacial acetic acidwas heated at 100 C for 20 min under microwave irradiation (Scheme1). Then, 20 mL of water was added, and the pH value was adjusted to 7.0 at room temperature [47-49]. The solution was filtered and dried ina vacuum to obtain a yellow precipitate. The product was purified in asilica gel column by using ethanol as eluent. The target compoundswere characterized by ESI-MS and 1H- and 13C NMR spectroscopy. | |
With ammonium acetate; glacial acetic acid; at 130℃; for 4h; | A cooled mixture of conc. H2SO4-HNO3 (60 mL, 2:1, v/v) was addedwith 1,10-phenanthroline (4 g, 22 mmol) and KBr (4 g, 33 mmol) andstirred at 130 C for 3 h. A yellow solution was cautiously neutralizedwith NaOH solution (10 molL 1) until its pH was neutral. The resultingmixture was extracted with CH2Cl2 and dried with anhydrous Na2SO4.Afterward, solvents were removed, and PDO was obtained as a yellowsolid. Then, PDO (0.420 g, 2 mmol), 4-carboxybenzaldehyde (0.360 g,2.4 mmol), and CH3COONH4 (3.2 g, 41.5 mmol) were mixed in 50 mL ofCH3COOH and stirred at 130 C for 4 h. After being cooled to roomtemperature, the solution was adjusted to pH 5.0 by adding NH3H2O(25 wt%) solution while stirring, and HNCP was dried in vacuum. HNCP(0.34 g, 0.79 mmol), 1,2-diaminobenzene (0.325 g, 3 mmol), 1-hydroxybenzotriazole(HOBT; 0.135 g, 1 mmol), N,Ndicyclohexylcarbodiimide(DCC; 0.248 g, 1.2 mmol), and triethylamine(167 μL) were dissolved in 30 mL of DMF at 4 C for 2 h whilestirring. The resulting mixture was stirred at room temperature for 24 hunder a N2 atmosphere. The faint yellow solid was filtered, washed withCH2Cl2 and Et2OH, and dried in vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.3% | With triethylamine; In ethanol; at 60℃; for 4h;Product distribution / selectivity; | To a solution of 4-formylbenzoic acid (250 mg, 1.67 mmol) in ethanol (5 mL) were added triethylamine (0.28 mL, 2.00 mmol) and <strong>[57497-39-9]N-tert-butylhydroxylamine hydrochloride</strong> (251 mg, 2.00 mmol). The mixture was then heated at 60° C. for 4 hours. The solvent was evaporated in vacuo and the residue purified by flash column chromatography on silica gel using 1percent acetic acid in ethyl acetate. The product was obtained as a white solid (320 mg, 1.56 mmol, 93.3percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | To a suspension of 4-formylbenzoic acid (4.00 g, 26.7 mmol) in dry DCM (8 mL) were added thionyl chloride (2.92 g, 40.0 mmol) and DMF (0.6 mL) dropwise at ambient temperature under nitrogen. The reaction mixture was refluxed for 2 h. After cooling, this mixture was added to 33% dimethylamine in water (10.5 mL, 72 mmol) dropwise over 15 min in an ice-water bath, and the reaction mixture stirred for 1 h at the same temperature. The solvent was evaporated in vacuums. The residue was purified by chromatography on silica gel to give the title compound (2.5 g, yield 53%) as a yellow solid. 1H-NMR (400 MHz, DMSO-d6) delta (ppm): 2.86 (s, 3H), 3.30 (s, 3H), 7.60 (d, J=7.6 Hz, 2H), 7.95 (d, J=7.6 Hz, 2H), 10.04 (s, 1H); LC-MS (ESI) m/z: 178 (M+1)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Example 101 A 4-Formyl-N,N-dimethylbenzamide[00685] To a suspension of 4-formylbenzoic acid (4.00 g, 26.7 mmol) in dry DCM (8 mL) were added thionyl chloride (2.92 g, 40.0 mmol) and DMF (0.6 mL) dropwise at ambient temperature under nitrogen. The reaction mixture was refluxed for 2 h. After cooling, this mixture was added to 33% dimethylamine in water (10.5 mL, 72 mmol) dropwise over 15 min in an ice-water bath, and the reaction mixture stirred for 1 h at the same temperature. The solvent was evaporated in vacuums. The residue was purified by chromatography on silica gel to give the title compound (2.5 g, yield 53%) as a yellow solid. ^-NMR (400 MHz, DMSO-i/6) 8(ppm): 2.86 (s, 3H), 3.30 (s, 3H), 7.60 (d, J= 7.6 Hz, 2H), 7.95 (d, J= 7.6 Hz, 2H), 10.04 (s, 1H); LC-MS (ESI) m/z: 178 (M+l)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; at 60℃; for 0.5h; | General procedure: A mixture of corresponding hydrazinylpyridazine 1 or 5 (1 mmol) and aldehyde 2 (1.1 mmol) in ethanol (5 mL) was heated at 60 oC for 0.5 h. The formation of hydrazone was checked by TLC and the reaction mixture was cooled to rt. Oxone (1.5 mmol) was added to the mixture at rt followed by tetramethyl ammonium bromide (0.2 mmol) and the resulting mixture was heated at 60 oC for another 5 h. The mixture was cooled to rt and extracted with dichloromethane (2 × 25 mL), dried over anhydrous sodium sulphate and concentrated to obtain a residue which was purified by column chromatography using hexane/ethyl acetate as eluent to furnish the desired triazolopyridazines 4 and 7. | |
In ethanol; at 60℃; for 0.5h; | General procedure: A mixture of corresponding hydrazinylpyridazine 1 or 5 (1 mmol) and aldehyde 2 (1.1 mmol) in ethanol (5 mL) was heated at 60 C for 0.5 h. The formation of hydrazone was checked by TLC and the reaction mixture was cooled to rt. Oxone (1.5 mmol) was added to the mixture at rt followed by tetramethyl ammonium bromide (0.2 mmol) and the resulting mixture was heated at 60 C for another 5 h. The mixture was cooled to rt and extracted with dichloromethane (2 × 25 mL), dried over anhydrous sodium sulfate and concentrated to obtain a residue which was purified by column chromatography using hexane/ethyl acetate as eluent to furnish the desired triazolopyridazines 4 and 7 (See reference no; 7 for supporting information). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 12h; | [0909] To a solution of AB-2 (1 g, 6.66 mmol, 1 eq), EDCI (1.53 g, 7.99 mmol, 1.2 eq), HOBt (900.03 mg, 6.66 mmol, 1 eq) and DIEA (3.44 g, 26.64 mmol, 4.64 mL, 4 eq) in DCM (15 mL) was added N-methylmethanamine (814.73 mg, 9.99 mmol, 915.43 muL, 1.5 eq, HCl) at 0C. The mixture was stirred at 20C. for 12 h to give a red solution. The completion of reaction was detected by TLC and LCMS. The reaction solution was diluted with DCM (40 mL), then washed with sat. aqu. NaHCO3 (30 mL) and brine (30 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=10/1 to 1:1) to give AG-3 . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16.0h; | [0914] To a solution of AI-1 (500 mg, 3.33 mmol, 1 eq) in DMF (5 mL) were added AI-2 (546.01 mg, 3.26 mmol, 9.78e-1 eq, HCl), DIEA (1.29 g, 9.99 mmol, 1.74 mL, 3 eq) and BOP (1.77 g, 4.00 mmol, 1.2 eq). The mixture was stirred at 20C. for 16 h to give a yellow solution. LCMS and TLC (eluting with: PE/EtOAc=1/1) showed the reaction was completed. The reaction mixture was quenched with H2O (20 mL) and extracted with MTBE (30 mL3). The organic layers were dried over Na2SO4 and concentrated to give the crude product. The product was purified by a flash column (eluting with:PE/EtOAc=5% to 50%) to give AI-3 . |