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CAS No. : | 380430-55-7 | MDL No. : | MFCD02258941 |
Formula : | C8H11BClNO4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | IDUSDMZTKZZVAW-UHFFFAOYSA-N |
M.W : | 231.44 | Pubchem ID : | 16427083 |
Synonyms : |
|
Chemical Name : | (2-Amino-4-(methoxycarbonyl)phenyl)boronic acid hydrochloride |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | 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 |
---|---|---|
8.5% | With sodium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 120℃; for 18.0h; | Sodium acetate (4.0 eq, 1.92 g, 23.41 mmol) and 1,1'- bis(diphenylphosphino)ferrocene palladium (II) chloride (complexed with dichloromethane) (0.05 eq, 214 mg, 0.29 mmol) were added to a mixture of methyl-5- bromopyrimidine-4-carboxylate (1.0 eq, 1.27 g, 5.85 mmol), and 2-amino-4- (methoxycarbonyl)phenylboronic acid hydrochloride (1.0 eq, 1.35 g, 5.85 mmol) in anydrous DMF (10 ml). The Mixture was stirred under nitrogen atmosphere at 1200C for 18 hours. Water and brine were added and the resulting solid impurities filtered off. The material was extracted with CH2Cl2 (4x) and the combined extracts dried over Na2SO4. After evaporation of CH2Cl2, the remaining DMF was evaporated by heating the residue in vacuo. The resulting solid was triturated in CH2Cl2, filtered and <n="76"/>dried to provide methyl 5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate as a beige solid (127 mg, 8.5percent yield). LCMS (ES): >80percent pure, m/z 256 [M+l]+; 1H NMR (DMSO-^6, 400 MHz) delta 3.79 (s, 3H), 7.81 (d, / = 8.0, IH), 8.68 (d, / = 8.8, IH), 9.49 (s, IH), 10.19 (s, IH), 12.37 (s, IH) ppm. |
8.5% | With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 18.0h; | Process 5 Sodium acetate (4.0 eq, 1.92 g, 23.41 mmol) and 1,1'-bis(diphenylphosphino)ferrocene palladium (II) chloride (complexed with dichloromethane) (0.05 eq, 214 mg, 0.29 mmol) were added to a mixture of methyl-5-bromopyrimidine-4-carboxylate (1.0 eq, 1.27 g, 5.85 mmol), and <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.0 eq, 1.35 g, 5.85 mmol) in anhydrous DMF (10 ml). The mixture was stirred under nitrogen atmosphere at 120° C. for 18 hours. Water and brine were added and the resulting solid impurities filtered off. The material was extracted with CH2Cl2 (4.x.) and the combined extracts dried over Na2SO4. After evaporation of CH2Cl2, the remaining DMF was evaporated by heating the residue in vacuo. The resulting solid was triturated in CH2Cl2, filtered and dried to provide methyl 5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate as a beige solid (127 mg, 8.5percent yield). LCMS (ES): >80percent pure, m/z 256 [M+1]+; 1H NMR (DMSO-d6, 400 MHz) delta 3.79 (s, 3H), 7.81 (d, J=8.0, 1H), 8.68 (d, J=8.8, 1H), 9.49 (s, 1H), 10.19 (s, 1H), 12.37 (s, 1H) ppm. |
With sodium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 120℃; for 18.0h;Inert atmosphere; | Sodium acetate (4.0 eq, 1.92 g, 23.41 mmol) and 1,1'-bis(diphenylphosphino)ferrocene palladium (II) chloride (complexed with dichloromethane) (0.05 eq, 214 mg, 0.29 mmol) were added to a mixture of methyl-5-bromopyrimidine-4-carboxylate (1.0 eq, 1.27 g, 5.85 mmol), and <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.0 eq, 1.35 g, 5.85 mmol) in anhydrous DMF (10 ml). The Mixture was stirred under nitrogen atmosphere at 120° C. for 18 hours. Water and brine were added and the resulting solid impurities filtered off. The material was extracted with CH2Cl2 (4.x.) and the combined extracts dried over Na2SO4. After evaporation of CH2Cl2, the remaining DMF was evaporated by heating the residue in vacuo. The resulting solid was triturated in CH2Cl2, filtered and dried to provide methyl 5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate as a beige solid (127 mg, 8.5percent yield). LCMS (ES): >80percent pure, m/z 256 [M+1]+; 1H NMR (DMSO-d6, 400 MHz) delta 3.79 (s, 3H), 7.81 (d, J=8.0, 1H), 8.68 (d, J=8.8, 1H), 9.49 (s, 1H), 10.19 (s, 1H), 12.37 (s, 1H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | With sodium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave; | Sodium acetate (3.0 eq, 240 mg, 2.93 mmol) and 1,1'- bis(diphenylphosphino)ferrocene palladium (II) chloride (complexed with dichloromethane) (0.05 eq, 36 mg, 0.049 mmol) were added to a mixture of methyl 5- bromo-2-(methylamino)pyrimidine-4-carboxylate (1.0 eq, 240 mg, 0.975mmol), and <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.0 eq, 226 mg, 0.98 mmol) in anydrous DMF (2 ml). The mixture was stirred under microwave heating at 1200C for 10 min. Addition of water induced precipitation of the expected compound that was filtered and dried, methyl 3-(methylamino)-5-oxo-5,6-dihydropyrimido[4,5- c]quinoline-8-carboxylate (57 mg, 21percent yield). LCMS (ES): >80percent pure, m/z 285 [M+l]+. |
With sodium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 120℃; for 18.0h; | Sodium acetate (3.0 eq, 240 mg, 2.93 mmol) and 1,1'-bis(diphenylphosphino)ferrocene palladium (II) chloride (complexed with dichloromethane) (0.05 eq, 36 mg, 0.049 mmol) were added to a mixture of methyl 5-bromo-2-(methylamino)pyrimidine-4-carboxylate (1.0 eq, 240 mg, 0.975 mmol), and <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.0 eq, 226 mg, 0.98 mmol) in anhydrous DMF (2 ml). The mixture was stirred under microwave heating at 120° C. for 10 min. Addition of water induced precipitation of the expected compound that was filtered and dried. methyl 3-(methylamino)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate (57 mg, 21percent yield). LCMS (ES): >80percent pure, m/z 285 [M+1]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10% | With sodium acetate; In N,N-dimethyl-formamide; at 120℃; for 0.666667h;Microwave; | In a microwave vessel, methyl 5-bromo-2-(methylthio)pyrimidine-4- carboxylate (1.0 eq, 274 mg, 1.18 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.2 eq, 329 mg, 1.42 mmol), and sodium acetate (3.0 eq, 291 mg, 3.55 mmol) were mixed in anhydrous DMF (2 ml). The mixture was degassed by bubbling nitrogen gas in the solution for 10 min and the reaction heated under microwaves at 1200C for 30 min. After cooling down the expected material crashed out of NMP. The solid was filtered, suspended in water filtered and dried. The material was triturated in AcOEt and filtered give a yellow solid. The same procedure was repeated 9 times using the same amounts of materials to provide methyl 3-(methylthio)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8- carboxylate (283 mg, 10% yield). LCMS (ES): >95% pure, m/z 302 [M+l]+, 1H NMR <n="82"/>(DMSO-d6, 400 MHz) delta 2.71 (s, 3H), 3.89 (s, 3H), 7.80 (dd, / = 1.6, / = 8.4, IH), 7.97 (d, / = 1.6, IH), 8.59 (d, / = 8.8, IH), 9.98 (s, IH), 12.34 (s, IH) ppm. |
10% | With sodium acetate; In N,N-dimethyl-formamide; at 120℃; for 0.666667h;Microwave irradiation; | Process 8 In a microwave vessel, methyl 5-bromo-2-(methylthio)pyrimidine-4-carboxylate (1.0 eq, 274 mg, 1.18 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.2 eq, 329 mg, 1.42 mmol), and sodium acetate (3.0 eq, 291 mg, 3.55 mmol) were mixed in anhydrous DMF (2 ml). The mixture was degassed by bubbling nitrogen gas in the solution for 10 min and the reaction heated under microwaves at 120 C. for 30 min. After cooling down the expected material crashed out of NMP. The solid was filtered, suspended in water filtered and dried. The material was triturated in AcOEt and filtered give a yellow solid. The same procedure was repeated 9 times using the same amounts of materials to provide methyl 3-(methylthio)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate (283 mg, 10% yield). LCMS (ES): >95% pure, m/z 302 [M+l]+, 1H NMR (DMSO-d6, 400 MHz) delta 2.71 (s, 3H), 3.89 (s, 3H), 7.80 (dd, J=1.6, J=8.4, 1H), 7.97 (d, J=1.6, 1H), 8.59 (d, J=8.8, 1H), 9.98 (s, 1H), 12.34 (s, 1H) ppm. |
10% | With sodium acetate; In N,N-dimethyl-formamide; at 120℃; for 0.666667h;Microwave irradiation; | In a microwave vessel, methyl 5-bromo-2-(methylthio)pyrimidine-4-carboxylate (1.0 eq, 274 mg, 1.18 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.2 eq, 329 mg, 1.42 mmol), and sodium acetate (3.0 eq, 291 mg, 3.55 mmol) were mixed in anhydrous DMF (2 ml). The mixture was degassed by bubbling nitrogen gas in the solution for 10 min and the reaction heated under microwaves at 120 C. for 30 min. After cooling down the expected material crashed out of NMP. The solid was filtered, suspended in water filtered and dried. The material was triturated in AcOEt and filtered give a yellow solid. The same procedure was repeated 9 times using the same amounts of materials to provide methyl 3-(methylthio)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate (283 mg, 10% yield). LCMS (ES): >95% pure, m/z 302 [M+1]+, 1H NMR (DMSO-d6, 400 MHz) delta 2.71 (s, 3H), 3.89 (s, 3H), 7.80 (dd, J=1.6, J=8.4, 1H), 7.97 (d, J=1.6, 1H), 8.59 (d, J=8.8, 1H), 9.98 (s, 1H), 12.34 (s, 1H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave; | In a microwave vessel, methyl 2-bromo-3-thiophene carboxylate (1.0 eq, 260 mg, 1.18 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.1 eq, 300 mg, 1.30 mmol), sodium acetate (3.0 eq, 292 mg, 3.56 mmol) and PdCl2(dppf) (0.05 eq, 31 mg, 0.059 mmol) were mixed together in anhydrous DMF (2 ml). The mixture was heated in a microwave oven at 1200C for 10 mn. Water was added and the solid filtered and dried. The material was suspended in CH2Cl2 , filtered and dried to afford methyl 4-oxo-4,5-dihydrothieno[3,2-c]quinoline-7-carboxylate as a yellow solid (152 mg, 50percent yield). LCMS (ES): 95percent pure, m/z 260 [M+l]+ ; <n="104"/>1H NMR (CDCl3, 400 MHz) delta 3. 99 (s, 3H), 7.54 (d, / = 5.2, IH), 7.79 (d, / = 4.8, IH), 7.86 (d, J = 8.4, IH), 7.91 (dd, J = 8.4, / = 1.6, IH), 8.03 (d, J = 1.2, IH) ppm. |
50% | With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave irradiation; | Process 11 In a microwave vessel, methyl 2-bromo-3-thiophene carboxylate (1.0 eq, 260 mg, 1.18 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.1 eq, 300 mg, 1.30 mmol), sodium acetate (3.0 eq, 292 mg, 3.56 mmol) and PdCl2(dppf) (0.05 eq, 31 mg, 0.059 mmol) were mixed together in anhydrous DMF (2 ml). The mixture was heated in a microwave oven at 120° C. for 10 nm. Water was added and the solid filtered and dried. The material was suspended in CH2Cl2, filtered and dried to afford methyl 4-oxo-4,5-dihydrothieno[3,2-c]quinoline-7-carboxylate as a yellow solid (152 mg, 50percent yield). LCMS (ES): 95percent pure, m/z 260 [M+1]+; 1H NMR (CDCl3, 400 MHz) delta 3.99 (s, 3H), 7.54 (d, J=5.2, 1H), 7.79 (d, J=4.8, 1H), 7.86 (d, J=8.4, 1H), 7.91 (dd, J=8.4, J=1.6, 1H), 8.03 (d, J=1.2, 1H) ppm. |
50% | With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave irradiation; | In a microwave vessel, methyl 2-bromo-3-thiophene carboxylate (1.0 eq, 260 mg, 1.18 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (1.1 eq, 300 mg, 1.30 mmol), sodium acetate (3.0 eq, 292 mg, 3.56 mmol) and PdCl2(dppf) (0.05 eq, 31 mg, 0.059 mmol) were mixed together in anhydrous DMF (2 ml). The mixture was heated in a microwave oven at 120° C. for 10 nm. Water was added and the solid filtered and dried. The material was suspended in CH2Cl2, filtered and dried to afford methyl 4-oxo-4,5-dihydrothieno[3,2-c]quinoline-7-carboxylate as a yellow solid (152 mg, 50percent yield). LCMS (ES): 95percent pure, m/z 260 [M+1]+; 1H NMR (CDCl3, 400 MHz) delta 3.99 (s, 3H), 7.54 (d, J=5.2, 1H), 7.79 (d, J=4.8, 1H), 7.86 (d, J=8.4, 1H), 7.91 (dd, J=8.4, J=1.6, 1H), 8.03 (d, J=1.2, 1H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave; | In a microwave vessel, methyl 5-bromothiazole-4-carboxylate (1.0 eq, 97 mg, 0.44 mmol), 2-amino-3-methoxycarbonyl phenyl boronic acid HCl (1.1 eq, 111 mg, 0.48 mmol), sodium acetate (3.0 eq, 107 mg, 1.31 mmol) and PdCl2(dppf) (0.05 eq, 11 mg, 0.022 mmol) were mixed together in anhydrous DMF (1 ml). The mixture was heated in a microwave oven at 1200C for 10 mn. Water was added and the material extracted with CH2CI2. The combined extracts wre washed with brine, dried over Na2SO4 and the solvents removed by evaporation. The material was dissolved in <n="159"/>a mixture of CH2CI2 and MeOH and the solution filtered through a pad of celite. Evaporation of the volatiles afforded crude methyl 4-oxo-4,5-dihydrothiazolo[4,5- c]quinoline-7-carboxylate as a black solid (44 mg, 39percent yield). A small part of the compound was subjected to preparative HPLC for analytical purpose. LCMS (ES): 95percent pure, m/z 261 [M+l]+. |
39% | With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave irradiation; | Process 24 In a microwave vessel, methyl 5-bromothiazole-4-carboxylate (1.0 eq, 97 mg, 0.44 mmol), 2-amino-3-methoxycarbonyl phenyl boronic acid HCl (1.1 eq, 111 mg, 0.48 mmol), sodium acetate (3.0 eq, 107 mg, 1.31 mmol) and PdCl2(dppf) (0.05 eq, 11 mg, 0.022 mmol) were mixed together in anhydrous DMF (1 ml). The mixture was heated in a microwave oven at 120° C. for 10 nm. Water was added and the material extracted with CH2Cl2. The combined extracts were washed with brine, dried over Na2SO4 and the solvents removed by evaporation. The material was dissolved in a mixture of CH2Cl2 and MeOH and the solution filtered through a pad of celite. Evaporation of the volatiles afforded crude methyl 4-oxo-4,5-dihydrothiazolo[4,5-c]quinoline-7-carboxylate as a black solid (44 mg, 39percent yield). A small part of the compound was subjected to preparative HPLC for analytical purpose. LCMS (ES): 95percent pure, m/z 261 [M+1]+. |
With sodium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 0.166667h;Microwave irradiation; | In a microwave vessel, methyl 5-bromothiazole-4-carboxylate (1.0 eq, 97 mg, 0.44 mmol), 2-amino-3-methoxycarbonyl phenyl boronic acid HCl (1.1 eq, 111 mg, 0.48 mmol), sodium acetate (3.0 eq, 107 mg, 1.31 mmol) and PdCl2(dppf) (0.05 eq, 11 mg, 0.022 mmol) were mixed together in anhydrous DMF (1 ml). The mixture was heated in a microwave oven at 120° C. for 10 nm. Water was added and the material extracted with CH2Cl2. The combined extracts were washed with brine, dried over Na2SO4 and the solvents removed by evaporation. The material was dissolved in a mixture of CH2Cl2 and MeOH and the solution filtered through a pad of celite. Evaporation of the volatiles afforded crude methyl 4-oxo-4,5-dihydrothiazolo[4,5-c]quinoline-7-carboxylate as a black solid (44 mg, 39percent yield). A small part of the compound was subjected to preparative HPLC for analytical purpose. LCMS (ES): 95percent pure, m/z 261 [M+1]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; for 0.666667h;Reflux; | A solution of methyl 4-chloronicotinate (1.68 g, 6.05 mmol), <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (3.17 g, 13.70 mmol), Cs2CO3 (8.90 g, 27.32 mmol), and PdCl2(dppf) (335 mg, 0.46 mmol) in dioxane (5percent H2O, 60 mL) was heated at reflux for 40 min. The reaction was cooled to rt, the precipitate was collected by filtration, and washed (dioxane, H2O, then with MeOH) to yield the desired lactam (2.07 g, 90percent). LCMS (ES): >95percent pure, m/z 255 [M+1]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;dmap; In acetonitrile; at 40℃; | A solution of <strong>[380430-55-7]2-amino-4-(methoxycarbonyl)phenylboronic acid hydrochloride</strong> (commercially available) (1.0 eq.), triethylamine (3.0 eq ), di-foert-butyl dicarbonate (1.1 eq ), and DMAP (0.1 eq.) in CH3CN (0.3 M) was stirred at 400C overnight. After cooling to ambient temperature, the reaction mixture was concentrated en vaccuo to obtain a crude residue. The crude material was purified by flash chromatography on a COMBIFLASH.(R). system (ISCO) using 0-30percent MeOH/DCM to give 2-(tert-butoxycarbonylamino)-4-(methoxycarbonyl)phenylboronic acid as a brown solid. |
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