(4S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane

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

実験手順: To a solution of (R,Z)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one oxime (86 g or Compound 61, 10.0 mg, 0.025 mmol) in dry DMF (1 mL) was added Cs2CO3 (12.2 mg, 0.0375 mmol) and the reaction mixture stirred at ambient temperature for 30 minutes. Then, (S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (86d, 7.68 mg, 0.03 mmol) was added and the reaction mixture stirred overnight. LCMS showed complete consumption of starting material. The reaction mixture was poured onto crushed ice and the resulting solid was filtered, rinsed with cold water, and dried to afford (R,Z)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime (86 h, 8.2 mg, 63%) as a light brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.33 (s, 3H) 1.39 (s, 3H) 1.91-2.01 (m, 4H) 2.72 (s, 3H) 3.07 (dd, J=16.55, 10.48 Hz, 1H) 3.26 (dd, J=17.05, 4.93 Hz, 1H) 3.55 (dd, J=7.96, 7.20 Hz, 1H) 3.90 (s, 3H) 4.05 (dd, J=7.96, 5.94 Hz, 1H) 4.10-4.21 (m, 3H) 4.89 (dd, J=10.61, 3.79 Hz, 1H) 6.74 (d, J=8.84 Hz, 1H) 7.01 (d, J=8.08 Hz, 1H) 7.11-7.22 (m, 2H) 7.61-7.69 (m, 2H)MS (ES) [M+H] calculated for C27H32FN6O4, 523.24. found 523.50. the reaction mixture stirred overnight consumption of starting material The reaction mixture was poured onto crushed ice the resulting solid was filtered rinsed with cold water dried

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

実験手順: To a solution of (R,Z)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one oxime (86 g or Compound 61, 10.0 mg, 0.025 mmol) in dry DMF (1 mL) was added Cs2CO3 (12.2 mg, 0.0375 mmol) and the reaction mixture stirred at ambient temperature for 30 minutes. Then, (S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (86d, 7.68 mg, 0.03 mmol) was added and the reaction mixture stirred overnight. LCMS showed complete consumption of starting material. The reaction mixture was poured onto crushed ice and the resulting solid was filtered, rinsed with cold water, and dried to afford (R,Z)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime (86 h, 8.2 mg, 63%) as a light brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.33 (s, 3H) 1.39 (s, 3H) 1.91-2.01 (m, 4H) 2.72 (s, 3H) 3.07 (dd, J=16.55, 10.48 Hz, 1H) 3.26 (dd, J=17.05, 4.93 Hz, 1H) 3.55 (dd, J=7.96, 7.20 Hz, 1H) 3.90 (s, 3H) 4.05 (dd, J=7.96, 5.94 Hz, 1H) 4.10-4.21 (m, 3H) 4.89 (dd, J=10.61, 3.79 Hz, 1H) 6.74 (d, J=8.84 Hz, 1H) 7.01 (d, J=8.08 Hz, 1H) 7.11-7.22 (m, 2H) 7.61-7.69 (m, 2H)MS (ES) [M+H] calculated for C27H32FN6O4, 523.24. found 523.50. the reaction mixture stirred overnight consumption of starting material The reaction mixture was poured onto crushed ice the resulting solid was filtered rinsed with cold water dried

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

実験手順: To a solution of (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one oxime (85c, 9.2 mg, 0.025 mmol) in dry DMF (1 mL) was added Cs2CO3 (12.2 mg, 0.0375 mmol) and the reaction mixture stirred at ambient temperature for 30 minutes. Then, (S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (85d, 7.68 mg, 0.03 mmol) was added and the reaction mixture stirred overnight. LCMS showed complete consumption of the starting material. The reaction mixture was poured onto crushed ice and the resulting solid was filtered and rinsed with cold water. Drying afforded (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime (7.8 mg, 63%) as a light brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 3H) 1.41 (s, 3H) 2.02 (qd, J=6.32, 3.03 Hz, 2H) 2.75 (s, 3H) 2.94 (dd, J=16.42, 8.84 Hz, 1H) 3.17 (dd, J=16.42, 4.55 Hz, 1H) 3.59 (dd, J=8.08, 7.07 Hz, 1H) 4.09 (dd, J=8.08, 6.06 Hz, 1H) 4.17-4.28 (m, 3H) 4.98 (ddd, J=8.72, 4.55, 1.64 Hz, 1H) 7.07 (td, J=8.27, 2.65 Hz, 1H) 7.34 (dd, J=8.08, 2.78 Hz, 1H) 7.43 (dd, J=8.72, 5.94 Hz, 1H). MS (ES) [M+H] calculated for C21H27BrFN5O3, 495.11. found 495.30. the reaction mixture stirred overnight consumption of the starting material The reaction mixture was poured onto crushed ice the resulting solid was filtered rinsed with cold water Drying

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

実験手順: To a solution of (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one oxime (85c, 9.2 mg, 0.025 mmol) in dry DMF (1 mL) was added Cs2CO3 (12.2 mg, 0.0375 mmol) and the reaction mixture stirred at ambient temperature for 30 minutes. Then, (S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (85d, 7.68 mg, 0.03 mmol) was added and the reaction mixture stirred overnight. LCMS showed complete consumption of the starting material. The reaction mixture was poured onto crushed ice and the resulting solid was filtered and rinsed with cold water. Drying afforded (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime (7.8 mg, 63%) as a light brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 3H) 1.41 (s, 3H) 2.02 (qd, J=6.32, 3.03 Hz, 2H) 2.75 (s, 3H) 2.94 (dd, J=16.42, 8.84 Hz, 1H) 3.17 (dd, J=16.42, 4.55 Hz, 1H) 3.59 (dd, J=8.08, 7.07 Hz, 1H) 4.09 (dd, J=8.08, 6.06 Hz, 1H) 4.17-4.28 (m, 3H) 4.98 (ddd, J=8.72, 4.55, 1.64 Hz, 1H) 7.07 (td, J=8.27, 2.65 Hz, 1H) 7.34 (dd, J=8.08, 2.78 Hz, 1H) 7.43 (dd, J=8.72, 5.94 Hz, 1H). MS (ES) [M+H] calculated for C21H27BrFN5O3, 495.11. found 495.30. the reaction mixture stirred overnight consumption of the starting material The reaction mixture was poured onto crushed ice the resulting solid was filtered rinsed with cold water Drying

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (S)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethanol (1.58 mL, 10.0 mmol) in CH2Cl2 (25 mL) was added DMAP (120 mg, 1.0 mmol) and triethylamine (2.08 mL, 15.0 mmol). The reaction mixture was cooled to 0° C. and methanesulfonyl chloride (12.0 mmol, 0.928 mL) was added slowly dropwise under N2 atmosphere. The reaction mixture was stirred for 2 h (monitored by TLC, 1:2 EtOAc-Hexanes). Saturated NH4Cl solution (20 mL) was added and the mixture was extracted with CH2Cl2. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to provide a yellow oil, which was dissolved in dry acetone (25 ml), followed by addition of NaI (7.5 g, 50 mmol). The reaction mixture was refluxed for 2 h (monitored by TLC, 1:4 EtOAc-Hexanes), cooled to room temperature and water (50 mL) was added. Extraction with ethyl acetate, washing of the combined organic layers with brine, drying over anhydrous Na2SO4, filtration and concentration provided a yellow oil, which was purified by flash chromatography (25% EtOAC-Hexane) to afford the title compound, (S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (0.82 g, 32% over two steps) as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.36 (s, 3H), 1.41 (s, 3H), 1.99-1.16 (m, 2H), 3.25 (dd, J=18.19, 8.84 Hz, 2H), 3.58 (t, J=7.20 Hz, 1H), 4.03-4.13 (m, 1H), 4.13-4.24 (m, 1H). MS (ES) [M+H] calculated for C7H14IO2, 257.00. found 257.08. the mixture was extracted with CH2Cl2 The combined organic layers were washed with brine dried over anhydrous Na2SO4 filtered concentrated to provide a yellow oil, which cooled to room temperature Extraction with ethyl acetate washing of the combined organic layers with brine drying over anhydrous Na2SO4, filtration and concentration provided a yellow oil, which was purified by flash chromatography (25% EtOAC-Hexane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (S)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethanol (1.58 mL, 10.0 mmol) in CH2Cl2 (25 mL) was added DMAP (120 mg, 1.0 mmol) and triethylamine (2.08 mL, 15.0 mmol). The reaction mixture was cooled to 0° C. and methanesulfonyl chloride (12.0 mmol, 0.928 mL) was added slowly dropwise under N2 atmosphere. The reaction mixture was stirred for 2 h (monitored by TLC, 1:2 EtOAc-Hexanes). Saturated NH4Cl solution (20 mL) was added and the mixture was extracted with CH2Cl2. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to provide a yellow oil, which was dissolved in dry acetone (25 ml), followed by addition of NaI (7.5 g, 50 mmol). The reaction mixture was refluxed for 2 h (monitored by TLC, 1:4 EtOAc-Hexanes), cooled to room temperature and water (50 mL) was added. Extraction with ethyl acetate, washing of the combined organic layers with brine, drying over anhydrous Na2SO4, filtration and concentration provided a yellow oil, which was purified by flash chromatography (25% EtOAC-Hexane) to afford the title compound, (S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (0.82 g, 32% over two steps) as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.36 (s, 3H), 1.41 (s, 3H), 1.99-1.16 (m, 2H), 3.25 (dd, J=18.19, 8.84 Hz, 2H), 3.58 (t, J=7.20 Hz, 1H), 4.03-4.13 (m, 1H), 4.13-4.24 (m, 1H). MS (ES) [M+H] calculated for C7H14IO2, 257.00. found 257.08. the mixture was extracted with CH2Cl2 The combined organic layers were washed with brine dried over anhydrous Na2SO4 filtered concentrated to provide a yellow oil, which cooled to room temperature Extraction with ethyl acetate washing of the combined organic layers with brine drying over anhydrous Na2SO4, filtration and concentration provided a yellow oil, which was purified by flash chromatography (25% EtOAC-Hexane)

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

実験手順: To a solution of (R,Z)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one oxime (86g or Compound 61, 10.0 mg, 0.025 mmol) in dry DMF (1 mL) was added Cs2CO3 (12.2 mg, 0.0375 mmol) and the reaction mixture stirred at ambient temperature for 30 minutes. Then, (5)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (86d, 7.68 mg, 0.03 mmol) was added and the reaction mixture stirred overnight. LCMS showed complete consumption of starting material. The reaction mixture was poured onto crushed ice and the resulting solid was filtered, rinsed with cold water, and dried to afford (R,Z)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime (86h, 8.2 mg, 63%) as a light brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.33 (s, 3H) 1.39 (s, 3H) 1.91-2.01 (m, 4H) 2.72 (s, 3H) 3.07 (dd, J=16.55, 10.48 Hz, 1H) 3.26 (dd, J=17.05, 4.93 Hz, 1H) 3.55 (dd, J=7.96, 7.20 Hz, 1H) 3.90 (s, 3H) 4.05 (dd, J=7.96, 5.94 Hz, 1H) 4.10-4.21 (m, 3H) 4.89 (dd, J=10.61, 3.79 Hz, 1H) 6.74 (d, J=8.84 Hz, 1H) 7.01 (d, J=8.08 Hz, 1H) 7.11-7.22 (m, 2H) 7.61-7.69 (m, 2H)MS (ES) [M+H] calculated for C27H32FN6O4, 523.24; found 523.50. the reaction mixture stirred overnight consumption of starting material The reaction mixture was poured onto crushed ice the resulting solid was filtered rinsed with cold water dried

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

実験手順: To a solution of (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one oxime (85c, 9.2 mg, 0.025 mmol) in dry DMF (1 mL) was added Cs2CO3 (12.2 mg, 0.0375 mmol) and the reaction mixture stirred at ambient temperature for 30 minutes. Then, (S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (85d, 7.68 mg, 0.03 mmol) was added and the reaction mixture stirred overnight. LCMS showed complete consumption of the starting material. The reaction mixture was poured onto crushed ice and the resulting solid was filtered and rinsed with cold water. Drying afforded (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime (7.8 mg, 63%) as a light brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 3H) 1.41 (s, 3H) 2.02 (qd, J=6.32, 3.03 Hz, 2H) 2.75 (s, 3H) 2.94 (dd, J=16.42, 8.84 Hz, 1H) 3.17 (dd, J=16.42, 4.55 Hz, 1H) 3.59 (dd, J=8.08, 7.07 Hz, 1H) 4.09 (dd, J=8.08, 6.06 Hz, 1H) 4.17-4.28 (m, 3H) 4.98 (ddd, J=8.72, 4.55, 1.64 Hz, 1H) 7.07 (td, J=8.27, 2.65 Hz, 1H) 7.34 (dd, J=8.08, 2.78 Hz, 1H) 7.43 (dd, J=8.72, 5.94 Hz, 1H). MS (ES) [M+H] calculated for C21H27BrFN5O3, 495.11; found 495.30. the reaction mixture stirred overnight consumption of the starting material The reaction mixture was poured onto crushed ice the resulting solid was filtered rinsed with cold water Drying

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (S)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethanol (1.58 mL, 10.0 mmol) in CH2Cl2 (25 mL) was added DMAP (120 mg, 1.0 mmol) and triethylamine (2.08 mL, 15.0 mmol). The reaction mixture was cooled to 0° C. and methanesulfonyl chloride (12.0 mmol, 0.928 mL) was added slowly dropwise under N2 atmosphere. The reaction mixture was stirred for 2 h (monitored by TLC, 1:2 EtOAc—Hexanes). Saturated NH4Cl solution (20 mL) was added and the mixture was extracted with CH2Cl2. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to provide a yellow oil, which was dissolved in dry acetone (25 ml), followed by addition of NaI (7.5 g, 50 mmol). The reaction mixture was refluxed for 2 h (monitored by TLC, 1:4 EtOAc—Hexanes), cooled to room temperature and water (50 mL) was added. Extraction with ethyl acetate, washing of the combined organic layers with brine, drying over anhydrous Na2SO4, filtration and concentration provided a yellow oil, which was purified by flash chromatography (25% EtOAC-Hexane) to afford the title compound, (S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (0.82 g, 32% over two steps) as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.36 (s, 3H), 1.41 (s, 3H), 1.99-1.16 (m, 2H), 3.25 (dd, J=18.19, 8.84 Hz, 2H), 3.58 (t, J=7.20 Hz, 1H), 4.03-4.13 (m, 1H), 4.13-4.24 (m, 1H). MS (ES) [M+H] calculated for C2H14IO2, 257.00; found 257.08. the mixture was extracted with CH2Cl2 The combined organic layers were washed with brine dried over anhydrous Na2SO4 filtered concentrated to provide a yellow oil, which cooled to room temperature Extraction with ethyl acetate washing of the combined organic layers with brine drying over anhydrous Na2SO4, filtration and concentration provided a yellow oil, which was purified by flash chromatography (25% EtOAC-Hexane)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In N,N-dimethylformamide (400 ml) were dissolved 6-methoxypyrido[2,3-b]pyrazin-3(4H)-one (14.53 g, 82.00 mmol) and (4S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (23.10 g, 90.20 mmol). Cesium carbonate (34.7 g, 1.06.6 mmol) was added to the solution and the mixture was stirred at 50° C. for 11 hours. After cooling in the air, water was added to the reaction solution and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to yield 22.58 g (90%) of the title compound in the form of a yellow orange oily product. was added to the reaction solution the mixture was extracted with ethyl acetate The extract was washed with saturated sodium chloride solution dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

実験手順: Triphenyl phosphine (31.0 g, 118.21 mmol) and imidazole (8.05 g, 118.21 mmol) were dissolved in a mixed solution (400 ml) of diethyl ether-acetonitrile (3:1), iodine (30.0 g, 118.21 mmol) was added thereto under cooling on ice and the mixture was stirred at room temperature for 3 hours. The solution was cooled on ice again, a mixed solution (100 ml) of (4S)-(+)-4-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxolane (15 g, 98.51 mmol) in diethyl ether-acetonitrile (3:1) was added thereto and stirred at room temperature for 18 hours. A saturated sodium thiosulfate aqueous solution was added to the reaction solution under cooling on ice and stirred for a while. The solution was extracted with diethyl ether and the extract was washed with saturated sodium chloride solution. The solvent was removed under reduced pressure and the obtained residue was triturated by adding a mixed solvent of ether/hexane to remove the insoluble material by filtration. The filtrate was concentrated under reduce pressure, and the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to yield 23.1 g (92%) of the title compound in the form of a colorless clear oily product. was added under cooling on ice The solution was cooled on ice again stirred at room temperature for 18 hours under cooling on ice stirred for a while The solution was extracted with diethyl ether the extract was washed with saturated sodium chloride solution The solvent was removed under reduced pressure the obtained residue was triturated by adding a mixed solvent of ether/hexane to remove the insoluble material by filtration The filtrate was concentrated the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

実験手順: To a solution of (R,Z)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one oxime (86 g or Compound 61, 10.0 mg, 0.025 mmol) in dry DMF (1 mL) was added Cs2CO3 (12.2 mg, 0.0375 mmol) and the reaction mixture stirred at ambient temperature for 30 minutes. Then, (S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (86d, 7.68 mg, 0.03 mmol) was added and the reaction mixture stirred overnight. LCMS showed complete consumption of starting material. The reaction mixture was poured onto crushed ice and the resulting solid was filtered, rinsed with cold water, and dried to afford (R,Z)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime (86 h, 8.2 mg, 63%) as a light brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.33 (s, 3H) 1.39 (s, 3H) 1.91-2.01 (m, 4H) 2.72 (s, 3H) 3.07 (dd, J=16.55, 10.48 Hz, 1H) 3.26 (dd, J=17.05, 4.93 Hz, 1H) 3.55 (dd, J=7.96, 7.20 Hz, 1H) 3.90 (s, 3H) 4.05 (dd, J=7.96, 5.94 Hz, 1H) 4.10-4.21 (m, 3H) 4.89 (dd, J=10.61, 3.79 Hz, 1H) 6.74 (d, J=8.84 Hz, 1H) 7.01 (d, J=8.08 Hz, 1H) 7.11-7.22 (m, 2H) 7.61-7.69 (m, 2H)MS (ES) [M+H] calculated for C27H32FN6O4, 523.24. found 523.50. the reaction mixture stirred overnight consumption of starting material The reaction mixture was poured onto crushed ice the resulting solid was filtered rinsed with cold water dried