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CAS No. : | 199609-62-6 | MDL No. : | MFCD06246052 |
Formula : | C12H18BNO4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | YHAQUGOSDQZIMA-UHFFFAOYSA-N |
M.W : | 251.09 | Pubchem ID : | 3684686 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280 | UN#: | N/A |
Hazard Statements: | H317 | Packing Group: | N/A |
GHS Pictogram: |
* 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 potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; N,N-dimethyl-formamide; at 100℃; for 0.5h;microwave irradiation; | EXAMPLE 227; 5-[3'-(aminomethyI)biphenyl-3-yl]-l,4-dihydroxy-l,8-naphthyridin-2-(l H)-one; Step 1 : ter/-butyl ({3'-[8-benzyloxy)-5-hydroxy-7-oxo-7,8-dihydro-l ,8-naphthyridin-4- yl]biphenyl-3-yl}methyl) carbamate; The Ethyl l-(benzyloxy)-5-( 3-bromophenyl)-4-hyroxy-2-oxo-l,2-dihydro-l,8- naphthyridine-3-carboxylate (Example 225, Step 4, 0.100 g3 0.202 mmol) was dissolved in DMF (5.0 mL) and H2O (1.0 mL). To this was added 3-(N-BOC-aminomethyl)phenylboronic acid (0.101 g, 0.404 mmol), potassium carbonate (0.084 g, 0.606 mmol), and the Pd dppf (DCM adduct) catalyst (0.008 g, 0.010 mmol) while N2 was bubbled through the solution. The reaction vessel was sealed and the reaction heated in a microwave at 1000C for 0.5 hour. The solution was cooled to room temperature, diluted with H2O ( 6 mL), and extracted into EtOAc (3x 10 mL). The organic layers were combined, dried, filtered, and concentrated. The residue was purified by SGC (0-50% EtOAc/hexane) to afford the title compound. ES MS: m/z = 622 (M + |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; N,N-dimethyl-formamide; at 100℃; for 0.166667h;microwave irradiation; | Step 2: tert-butyl [(3'-[l-(benzyloxy)-2-oxo-l,2-dihyrdo-l,8-naphmvridm-4- yl]methyl}biphenyl-3-yl)methyl]carbamate; The l-(benzyloxy)-4-(3-bromobenzyl)-l,8-naphthyridin-2(l H)-one (0.150 g, 0.356 mmol) was dissolved in DMF (5.0 mLs) and H2O (1.0 mL). To this was added 3-(N-BOC- aminomethyl)phenylboronic acid (0.179 g, 0.712 mmol), potassium carbonate (0.148 g, 1.068 mmol), and the Pd dppf (DCM adduct) catalyst (0.015 g, 0.018 mmol) while N2 was bubbled through the solution. The reaction vessel was sealed and the reaction heated in a microwave at 100 0C for 10 minutes. The solution was cooled to room temperature, diluted with aqueous HCl (IN, 6 mL), and extracted into EtOAc (10 mL). The organic layer was dried, filtered, and concentrated. ES MS: m/z - 548 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; N,N-dimethyl-formamide; at 100℃; for 0.5h;microwave irradiation; | Step 2: ethyl 1 -(benzyloxy)-5-[(3'-[(tert-butoxycarbonyl)amino]methyl}biphenyl-3- yl)methyl]-4-hydroxy-2-oxo-l ,2-dihydro-l, S-naphthyridine-S-carboxylate.; Ethyl l-(benzyloxy)-5-(3-bromoben2yl)-4-hydroxy-2-oxo-l,2-dihydro-l,8- naphthyridine-3-carboxylate: from step 1 (0.200 g, 0.41 mmol) was dissolved in DMF (5.0 mL) and H2O (1.0 mL). To this was added 3-(N-BOC-aminomethyl)phenylboronic acid (0.101 g, 0.404 mmol), K2CO3 (0.084 g, 0.606 mmol), and the Pd dppf (DCM adduct) catalyst (0.008 g,0.010 mmol) while N2 was bubbled through the solution. The reaction vessel was sealed and the reaction heated in a microwave at 1000C for 0.5 hour. The solution was cooled to room temperature, diluted with H2O (6 mL), and extracted into EtOAc (3x 10 mL). The organic layers were combined, dried, filtered, and concentrated. The residue was purified by SGC (0-100% EtOAc/hexane) to afford the title compound (150 mgs). ES MS: m/z = 636.1 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
For compounds (2-6) the commercially available 4-aminomethylphenylboronic acid and 3-aminomethylphenylboronic acid were BOC protected under standard conditions (Wei et al., 2000) and the appropriate boronic acid was used at the Suzuki coupling stage in the synthesis of compounds (2-6). The BOC group was removed with 4 M HCl in dioxane at RT after hydrazone coupling; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In erthanol; water; toluene; at 95℃; for 0.5h; | Example A9; 7-[3-(aminomethyl)phenyl]-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-4-amine trifluoroacetate salt; A9.1: 4-Chloro-7-[3-(t-butyloxycarbonylaminomethyl)phenyl]-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridine; A mixture of A2.8 (620 mg; 2.05 mmol), 3-(N-Bocaminomethyl)phenylboronic acid, [purchased from Frontier Scientific] (652 mg; 2.60 mmol), tetrakis(triphenylphosphine)palladium(0) (60 mg; 0.048 mmol), 2M Na2CO3 (4 ml), ethanol (5 ml) and toluene (8 ml) was vigorously stirred at 95 C. for 0.5 hr. After cooling to rt, the reaction mixture was partitioned between ethyl acetate (100 ml) and water (25 ml). After drying (MgSO4), the organic layer was concentrated to afford a yellow oil, that was chromatographed on a 5×15 cm silica gel column using a stepwise gradient from 100% dichloromethane to 3% methanol in dichloromethane. The purest fractions were concentrated to afford 729 mg (83%) of A9.1 as a light yellow foam. 1H-NMR (CDCl3) δ: 7.97 (1H, s), 7.82 (1H, s), 7.63 (2H, m), 7.44 (2H, t, J=7.5 Hz), 7.33 (1H, d, J=7.5 Hz), 4.95 (1H, m), 4.40 (2H, d, J=5.5 Hz), 4.16 (3H, s), 1.48 (9H, s) HPLC (A): 99%, ret. time 1.86 min., LC/MS (M+H)+=429.12 (431.12). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; ethanol; water; at 100℃; for 0.833333h; | Example A44; rr3-r8-methyl-5-(methylamino')-8H-imidazor4.5-dlthiazolo[4,5-b]pyridin-2- yllphenyllmethyll carbamic acid 1,1 -dimethyl ethyl ester; A44A3.3 (25 mg, 0.084 mmol), 3-(t-butyloxycarbonylaminomethyl)phenylboronic acid (21 mg, 0.085 mmol) and tetrakis(triphenylphosphine)palladium (0) (9.7mg, 0.008 mmol) was added to a mixture of 2M aqueous sodium carbonate (0.18 mL) dioxane83 EPO <DP n="85"/>(0.40 mL) and ethanol (0.40 mL). The reaction mixture was heated under argon for 50 minutes at 100 0C. The reaction mixture allowed to cool to room temperature and the solvents were removed under reduced pressure. Water (6 mL) was added and placed in an ice bath. The precipitate was collected by filtration, washed with additional water and dried under vacuum. The solid was rinsed with hexane to yield 38.8 mg of a tan solid. The crude product was purified by flash silica gel column chromatography (98:2 ethyl acetate/methanol -^ 50:48:1:1 THF/ethyl acetate/methanol/ammonium hydroxide -> 50:45:3:2 THF/ethyl acetate/methanol/ammonium hydroxide. Fractions for which the desired mass were obtained were combined and the solvent removed under reduced pressure. The solid was suspended in hexane, filtered and rinsed with additional hexane. The solid was then triturated with a mixture of 90:10 ether/ethyl acetate to yield 10.4 mg of the desired product as a pale yellow solid. M+H+ = 425.24. 1H NMR 400 MHz ^6DMSO 5 8.24 s, IH, 8.06-7.90 m, 2H, 7.60-7.48, m, 2H, 7.40 br s, 1 H, 7.10 br s, IH, 4.24 br s, 2H, 4.06, s, 3H, 3.06, br s, 3H, 1.48 s, 9H. |
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