Structure of 330793-45-8
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CAS No. : | 330793-45-8 |
Formula : | C13H12BNO3 |
M.W : | 241.05 |
SMILES Code : | OB(O)C1=CC=C(C=C1)C(=O)NC1=CC=CC=C1 |
MDL No. : | MFCD04115683 |
InChI Key : | DAUSGSRIYCUJDK-UHFFFAOYSA-N |
Pubchem ID : | 11096747 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P264-P271-P302+P352-P305+P351+P338-P362-P403+P233-P501 |
* 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 |
---|---|---|
63% | With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; at 20℃; | To a mixture of 4-carboxyphenyl boronic acid (0.200 g, 1. 21 mmol), aniline (0.13 mL, 1. 45 mmol) and triethylamine (0.34 ML, 2.41 mmol) in dichloromethane (3 mL) was added benzotriazole-l-yl-oxy-tris (pyrrolidine) -phosphonium hexafluoro- phosphate (0.753 g, 1.45 mmol) at room temperature, and the stirring was continued overnight. The mixture was diluted with water and extracted with ethyl acetate. The separated organic phase was washed with saturated sodium carbonate solution and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by recrystallization from ethyl acetate to give [4- (anilinocarbonyl) phenyl] boronic acid (0.183 g, 63%) as a colorless solid. |
42% | General procedure: Toluene (25 mL) and activated 4A molecular sieve beads (0.5 g) were added to a solution of 3-CPBA or 4-CPBA (166 mg, 1 mmol) in MeOH (3 mL) and the mixture was magnetically stirred at 60 C for 1h. APTES (0.468 mL, 2 mmol) was then added and the mixture was stirred at 60 C for additional 24 h followed by the filtration through a pad of Celite 545 and evaporation of the solvent on a rotary evaporator. The oily residue was suspended in 0.5 M aqueous HCl (20 mL) and the product was extracted with EtOAc (3×30 mL). The combined organic layers were washed with distilled water (3 ×20 mL) until neutral pH, dried with anhydrous MgSO4, filtered and the solvent was evaporated to afford I (292 mg, 79 %) or II (306 mg, 83 %) as white solid with purity higher than 95 % (according to 1H NMR data) | |
40.8% | With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 12h; | General procedure: A suspension of 3-boronobenzoic acid (1.0 g, 5.9 mmol), aniline (0.65 g, 7 mmol), Et3N (1.29 g, 12 mmol) and PyBop (3.6 g, 7 mmol) in DMF(10 mL) was stirred for 12 h at r t. After completion of reaction, the solution was diluted with H2O (15 mL), and then the product was extracted three times with EtOAc (50 mL). The combined organic layer was dried over Na2SO4, and the solvent was removed in vacuo, the crude product was purified on a silica gel column using (1-5%) CH3OH/DCM as eluent to afford 16a (1.47 g, 75%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | 4-Phenylaminocarbonylphenylboronic acid (19d). White solid (67% yield by mass): 1H NMR (300 MHz, 5% D2O in CD3OD) δ7.87 (s, 4 H), 7.69-7.65 (m, 2 H), 7.39-7.32 (m, 2 H), 7.14 (m, 1 H); 13C NMR (100 MHz, 5% D2O in CD3OD) δ169.1, 139.7, 137.6, 135.0, 129.8, 127.6, 125.7, 122.4; IR (microscope) 3301, 3042, 1643, 1537 cm-1; HRMS (ES, m/z) calcd for C13H13BNO3 (M+H)+242.0983, found 242.0984. | |
40.8% | With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃; | General procedure: Weigh 3-carboxybenzeneboronic acid (1. 0g, 5 · 9mmol), aniline (0 · 65g, 7mmol), Et3N (1 · 29g, 12mmol), 1Η-benzotriazol-1-yloxy Pyrrolidinyl hexafluorophosphate (3.6 g, 7 mmol) was placed in 10 ml of DMF and stirred at room temperature overnight. After completion of the reaction, the mixture was washed with saturated NH4C1 and ethyl acetate.The product was concentrated (1.47 g, 75%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With hydrogenchloride; In tetrahydrofuran; hexane; | b 4-(Anilinocarbonyl)phenylboronic acid n-Butyl lithium (1.6 M in hexane solution, 5.7 ml, 9.05 mmol) was added slowly to a solution of N1-phenyl-4-bromo-2-methoxybenzamide (1.0 g, 3.62 mmol) in tetrahydrofuran (27 mL) at -78 C. After 30 minutes, triisopropyl borate (1.25 mL, 5.43 mmol) was added rapidly. The reaction mixture was allowed to warm up to room temperature after 13 minutes and stirred for 6 hours. Hydrochloric acid (2.5N, 27 mL) was added and the mixture was stirred overnight. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The residue was re-crystallized from ethyl acetate/heptane to give 4-(anilinocarbonyl)phenylboronic acid (0.354 g, 40%). 1H NMR (DMSO-d6) δ 7.10 (m, 1H), 7.35 (m, 2H), 7.80 (m, 4H), 7.92 (m, 2H), 8.23 (s, 2H), 10.23 (s, 1H). |
40% | With hydrogenchloride; In tetrahydrofuran; hexane; | b) 4-(Anilinocarbonyl)phenylboronic acid n-Butyl lithium (1.6 M in hexane solution, 5.7 ml, 9.05 mmol) was added slowly to a solution of N1-phenyl-4-bromo-2-methoxybenzamide (1.0 g, 3.62 mmol) in tetrahydrofuran (27 mL) at -78 C. After 30 minutes, triisopropyl borate (1.25 mL, 5.43 mmol) was added rapidly. The reaction mixture was allowed to warm up to room temperature after 13 minutes and stirred for 6 hours. Hydrochloric acid (2.5N, 27 mL) was added and the mixture was stirred overnight. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The residue was re-crystallized from ethyl acetate/heptane to give 4-(anilinocarbonyl)phenylboronic acid (0.354 g, 40%). 1H NMR (DMSO-d6) δ 7.10 (m, 1H), 7.35 (m, 2H), 7.80 (m, 4H), 7.92 (m, 2H), 8.23 (s, 2H), 10.23 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With ammonium hydroxide; sodium carbonate; In methanol; 1,2-dimethoxyethane; dichloromethane; water; | c cis-N1-Phenyl-4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl] 1H-pyrazolo[3,4-d]pyrimidin-3-yl}benzamide cis-3-Iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.226 mmol), 4-(anilinocarbonyl)phenylboronic acid (60 mg, 0.249 mmol), palladium tetrakistriphenyphosphine(16 mg, 0.014 mmol) and sodium carbonate (58 mg, 0.544 mmol) were mixed with ethylene glycol dimethyl ether (3mL) and water (1.5 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was by preparative thin layer column chromatography using dichloromethane/methanol/ammonium hydroxide (95:5:05) as mobile phase to give cis-Ni-phenyl-4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}benzamide (32 mg, 27%). 1H NMR (DMSO-d6) 6 1.60 (m, 4H), 1.73 (m, 2H), 2.08 (m, 2H), 2.19 (s, 3H), 2.28 (m, 11H), 4.84 (m, 1H), 7.12 (m, 1H), 7.38 (m, 2H), 7.81 (m, 4H), 8.16 (d, J=8.30 Hz, 2H), 8.27 (s, 1H), 10.34 (s, 1H). LC/MS (Micromass-Column: Pecosphere, C18, 3 um, 33*4.6 mm. Eluents: 0% B/A to 100% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 3.5 mL/min.): MH+=511.2, Rt=2.41 min. |
27% | With ammonium hydroxide; sodium carbonate; In methanol; 1,2-dimethoxyethane; dichloromethane; water; | c) cis-N1-Phenyl-4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}benzamide cis-3-Iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.226 mmol), 4-(anilinocarbonyl)phenylboronic acid (60 mg, 0.249 mmol), palladium tetrakistriphenyphosphine(16 mg, 0.014 mmol) and sodium carbonate (58 mg, 0.544 mmol) were mixed with ethylene glycol dimethyl ether (3 mL) and water (1.5 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was by preparative thin layer column chromatography using dichloromethane/methanol/ammonium hydroxide (95:5:05) as mobile phase to give cis-N1-phenyl-4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}benzamide (32 mg, 27%). 1H NMR (DMSO-d6) δ 1.60 (m, 4H), 1.73 (m, 2H), 2.08 (m, 2H), 2.19 (s, 3H), 2.28 (m, 11H), 4.84 (m, 1H), 7.12 (m, 1H), 7.38 (m, 2H), 7.81 (m, 4H), 8.16 (d, J=8.30 Hz, 2H), 8.27 (s, 1H), 10.34 (s, 1H). LC/MS (Micromass-Column: Pecosphere, C18, 3 um, 33*4.6 mm. Eluents: 0% B/A to 100% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 3.5 mL/min.): MH+=511.2, Rt=2.41 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.1% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃;Inert atmosphere; | General procedure: A solution of 3-bromothieno[3,2-c]pyridin-4-amine (3 g, 13 mmol), Pd(PPh3)4 (1.5 g, 1.3 mmol) and (4-phenoxyphenyl)boronic acid (3.06 g, 14.3 mmol) in toluene (20 mL) was degassed with nitrogen for 5 min followed by addition of EtOH (4 mL), H2O (2 mL) and Na2CO3 (3.5 g, 32.5 mmol) under continuous flow of nitrogen. The reaction mixture was stirred at 90 C for 2 h. The reaction mixture was cooled, filtered through Celite, diluted with water (45 mL), and extracted with (3 * 60 mL) ethyl acetate. The combined organic layers were dried over sodium sulfate and were concentrated in vacuo, the crude product was purified on a silica gel column using (20-80% ethyl acetate/hexanes) as eluent to afford 10 (4.0 g, 96%) as a white solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | General procedure: To a solution of 12 (1 equiv) in dioxane and water (5:1) was added boronic acid (1.2 equiv) followed by addition of cesium carbonate (1 equiv) and PdCl2(dffp) (0.1 equiv). The reaction mixture was degassed and heated at 80C overnight. The reaction was diluted with EtOAc and washed with water (2). After drying over Na2SO4, filtration and concentration, the crude product was dissolved in DCM (4 ml) and TFA (8 ml) was added. The reaction was stirred for 4 h at rt followed by concentration. The residue was dissolved in DCM and washed with 10% Na2CO3 (2), the organic layer was dried (MgSO4), filtered and concentrated. The crude product was purified by flash column chromatography (80% EtOAc/Hex) or recrystallization from DCM/Hexane or by prep TLC (EtOAc) to give the desired product |
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