4-bromo-2-(diethoxymethyl)furan

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared according to procedure B from 4,4-dimethyl 2 oxo-1,4-dihydro 2H-benzo[d][1,3]oxazin-6-boronic acid and 3-bromo-5-Diethoxymethyl furan. A brown gum: 1H NMR (DMSO-d6) δ 10.2 (s, 1H), 8.12 (s, 1H), 7.54-7.49 (m, 2H), 6.93-6.88 (m, 2H), 5.56 (s, 1H), 3.60-3.38 (m, 4H), 1.67 (s, 6H), 1.2-1.14 (m, 6H). MS (ESI) m/z 344 [M−H]−. Anal. Calcd. For C19H23NO5.1/2 H2O: C, 64.39; H, 6.77; N, 3.95. Found C, 64.90; H, 6.79; N, 3.78. Prepared

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared according to procedure B from 4,4-dimethyl 2 oxo-1,4-dihydro 2H-benzo[d][1,3]oxazin-6-boronic acid and 3-bromo-5-Diethoxymethyl furan. A brown gum: 1H NMR (DMSO-d6) δ 10.2 (s, 1H), 8.12 (s, 1H), 7.54-7.49 (m, 2H), 6.93-6.88 (m, 2H), 5.56 (s, 1H), 3.60-3.38 (m, 4H), 1.67 (s, 6H), 1.2-1.14 (m, 6H). MS (ESI) m/z 344 [M−H]−. Anal. Calcd. For C19H23NO5.1/2 H2O: C, 64.39; H, 6.77; N, 3.95. Found C, 64.90; H, 6.79; N, 3.78. Prepared

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: An amount of 1.0 g (4.1 mmol) of 4-bromo-2-(diethoxymethyl)furan, is dissolved in ether (15 mL) and cooled to −78° C. To this is added 4.3 mL (6.02 mmol) of sec-butyllithium. After stirring at −78° C. for 30 minutes, triisopropyl borate (1.10 mL, 5.01 mmol) is added dropwise. The mixture is stirred at −78° C. for 1.5 hours and brought to room temperature for 2 hours. The mixture is hydrolyzed with 2N HCl and stirred at room temperature for 1 hour. The ether layer is separated and the water layer is washed once more with ether. The combined ether layers is washed once with brine and dried with sodium sulfate. Evaporated to give 563 mg of the boronic acid as dark oil. The mixture is stirred at −78° C. for 1.5 hours brought to room temperature for 2 hours stirred at room temperature for 1 hour The ether layer is separated the water layer is washed once more with ether The combined ether layers is washed once with brine dried with sodium sulfate Evaporated

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: An amount of 1.0 g (4.1 mmol) of 4-bromo-2-(diethoxymethyl)furan, is dissolved in ether (15 mL) and cooled to −78° C. To this is added 4.3 mL (6.02 mmol) of sec-butyllithium. After stirring at −78° C. for 30 minutes, triisopropyl borate (1.10 mL, 5.01 mmol) is added dropwise. The mixture is stirred at −78° C. for 1.5 hours and brought to room temperature for 2 hours. The mixture is hydrolyzed with 2N HCl and stirred at room temperature for 1 hour. The ether layer is separated and the water layer is washed once more with ether. The combined ether layers is washed once with brine and dried with sodium sulfate. Evaporated to give 563 mg of the boronic acid as dark oil. The mixture is stirred at −78° C. for 1.5 hours brought to room temperature for 2 hours stirred at room temperature for 1 hour The ether layer is separated the water layer is washed once more with ether The combined ether layers is washed once with brine dried with sodium sulfate Evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared according to procedure B from 4,4-dimethyl 2 oxo -1,4-dihydro 2H-benzo[d][1,3]oxazine-6-boronic acid and 3-bromo-5-diethoxymehyl furan. A brown gum: 1H NMR (DMSO-d6) δ10.2 (s, 1H), 8.12(s, 1H), 7.54-7.49 (m, 2H), 6.93-6.88(m, 2H), 5.56(s, 1H), 3.60-3.38(m, 4H), 1.67(s ,6H), 1.2-1.14 (m, 6H). .MS (ESI) m/z 344 [M−H]−. Anal. Calcd. For C19H23NO51/2 H2O: C, 64.39; H, 6.77; N, 3.95. Found C, 64.90; H, 6.79; N, 3.78. Prepared

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-(2,4-dichloro-5-methoxyanilino)-7-iodo-6-methoxy-3-quinolinecarbonitrile (3.5 g, 7.00 mmol), tributyl [5-(diethoxymethyl)-3-furanyl]stannane (generated from reaction of 4-bromo-2-(diethoxymethyl)-furan [ref. Chiarello, J, Joullie, M. M., Tetrahedron, 44(1), 41-48 (1988)] with tributyl tin chloride in the presence of n-BuLi) (5.76 g, 12.55 mmol), and dichlorobis(triphenylphosphine)pallidium (II) (100 mg) in 80 mL of dioxane is heated at reflux for 5 hours. Additional dichlorobis(triphenylphosphine)pallidium (II) (100 mg) is added and the reaction mixture is heated at reflux overnight. The reaction mixture is partitioned between ethyl acetate and water. The insoluble material is collected by filtration to provide 1.09 g of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-[5-(diethoxymethyl)-3-furyl]-6-methoxy-3-quinolinecarbonitrile as a pale green solid; 1H NMR (DMSO-d6) δ 1.18 (t, J=7 Hz, 6H), 3.63 (q, J=7 Hz, 4H), 3.87 (s, 3H), 4.07 (s, 3H), 5.60 (s, 1H), 7.13 (s, 1H), 7.37 (s, 1H), 7.76 (s, 1H), 7.95 (s, 1H), 8.15 (s, 1H), 8.35 (s, 1H), 8.45 (s, 1H), 9.84 (s, 1H); MS 542.1, 544.1 (M+H)+. is heated at reflux for 5 hours the reaction mixture is heated at reflux overnight The reaction mixture is partitioned between ethyl acetate and water The insoluble material is collected by filtration

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared according to procedure B from 4,4-dimethyl 2 oxo-1,4-dihydro 2 H-benzo [d][1,3]oxazine -6-boronic acid and 3-bromo-5-diethoxymethyl furan. A brown gum: 1H NMR (DMSO-d6) δ10.2 (s, 1H), 8.12(s, 1H), 7.54-7.49 (m, 2H), 6.93-6.88(m, 2H), 5.56(s, 1H), 3.60-3.38(m, 4H), 1.67(s ,6H), 1.2-1.14 (m, 6H). MS (ESI) m/z 344 [M−H]−. Anal. Calcd. For C19H23NO5.½ H2O: C, 64.39; H, 6.77; N, 3.95. Found C, 64.90; H, 6.79; N, 3.78. Prepared

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared according to procedure B from 4,4-dimethyl 2 oxo-1,4-dihydro 2H-benzo[d][1,3]oxazin-6-boronic acid and 3-bromo-5-Diethoxymethyl furan. A brown gum: 1H NMR (DMSO-d6) δ 10.2 (s, 1H), 8.12 (s, 1H), 7.54-7.49 (m, 2H), 6.93-6.88 (m, 2H), 5.56 (s, 1H), 3.60-3.38 (m, 4H), 1.67 (s, 6H), 1.2-1.14 (m, 6H). MS (ESI) m/z 344 [M−H]−. Anal. Calcd. For C19H23NO5.1/2 H2O: C, 64.39; H, 6.77; N, 3.95. Found C, 64.90; H, 6.79; N, 3.78. Prepared