Herein we wish to record our attempts in this respect (Shape 2). Open in another window Figure 2 Scaffolds useful for the structural marketing predicated on BMS-777607 with this paper. 2. in 92% produce. Alternatively, deprotonation of substance 2 with sodium hydride, accompanied by treatment with an alkyl halide (MeI, EtBr, or IC50 (M)IC50 (M)(2). 1-Fluoro-4-iodobenzene (2.22 g, 10 mmol) and piperidin-2-one (1.2 g, 12 mmol) had been added to dried out DMF (30 mL), accompanied by the addition of K3PO4 (6.36 g, 30 mmol) and CuI (190 mg, 0.1 mmol). The blend was warmed to 100 C for 12 h before filtering through Celite. After cleaning with ethyl acetate (3 10 mL), the mixed organic stage was concentrated as well as the residue was purified by column chromatography to provide 1-(4-fluorophenyl)piperidin-2-one (1.73 g, 90%) like SCR7 pyrazine a yellowish solid. This = 10.6, 6.7 Hz, CH), 3.83 (d, 1 H, = 6.7 Hz, CHH), 3.70C3.61 (m, 1H, CHH), 3.58 (t, 1 H, = 6.9 Hz, CH), 2.32C2.24 (m, 1H, CHH), 2.23C2.16 (m, 1H, CHH), 2.12C2.04 (m, 1H, CHH), 2.02C1.87 (m, 2H, CH, CHH), 0.94 (d, 6 H, = 6.6 Hz, CH3); 13C-NMR (150 MHz, CDCl3) 171.0, 166.3, 162.1, 160.4, 138.8, 127.9, 116.2, 100.0, 71.5, 51.6, 49.6, 27.8, 25.3, 21.4, 19.1; HR-MS (ESI) Calcd for C16H21FNO3 [M + H]+ 294.1506, Found out 294.1518. (3). To a remedy of 2 (217 mg, 0.74 mmol) in THF/MeOH/H2O (1/1/1, 3 mL altogether) in 0 C was added LiOH monohydrate (94 mg, 2.2 mmol). The response blend was warmed to space temp and stirred for 5 h. The perfect solution is was acidified to pH 1 with 1 mol/L HCl and extracted with EtOAc (3 20 mL). The organic components had been combined and cleaned with brine (2 5 mL). Evaporation from the solvent offered the corresponding acidity 3 (152 mg, 87%) like a white solid. 1H-NMR (600 MHz, CDCl3) 7.33C7.28 (m, 1H, ArH), 7.25C7.19 (m, 1H, ArH), 3.69C3.55 (m, 2H, NCH2), 3.43 (dd, 1H, = 8.2, 6.5 Hz, CH), 2.16C2.10 (m, 1 H, CHH), 2.08C2.02 (m, 1H, CHH), 1.98C1.91 (m, 1H, CHH), 1.91C1.83 (m, 1H, CHH); 13C-NMR (150 MHz, CDCl3) 174.3, 170.2, 161.3, 159.6, 138.7, 127.9, 115.6, 51.8, 50.3, 27.5, 21.6; HR-MS (ESI) Calcd for C12H13FNO3 238.0880 [M + H]+, found 238.0910. (4). To a remedy of acidity 3 (220 mg, 0.93 mmol) in Et2O (5 mL) was added liquid Br2 (48 L, 0.93 mmol) at 0 C. The response blend was stirred for 2 h before focused = 12.1, 4.6 Hz, NCHH), 3.82 (ddt, 1H, = 13.0, 6.3, 2.4 Hz, NCHH), 2.77C2.69 (m, 1H, CH(5a). 87% produce; 1H-NMR (600 MHz, CDCl3) 7.25C7.19 (m, 1 H, ArH), 7.12C7.01 (m, 1H, ArH), 4.06C3.88 (m, 2H, OCH2), 3.78C3.58 (m, 1H, CH= 2.4 Hz, CH3), 0.97 (d, 3H, = 2.0 HzCH3), 0.96 (d, 3H, = 2.1 Hz, CH3); 13C-NMR (150 MHz, CDCl3) 173.8, 170.1, 161.9, 160.2, 139.3, 127.8, 116.0, 115.9, 71.5, 51.9, 51.3, 33.6, 27.8, 22.9, 20.4, 19.2; HR-MS (ESI) Calcd for C17H23FNO3 308.1662 [M + H]+, found 308.1599. (5b). 76% produce; 1H-NMR (600 MHz, CDCl3) 7.24C7.18 (m, 2H, ArH), 7.08C7.03 (m, 2H, ArH), 4.01C3.90 (m, 2H, OCH2), 3.72C3.65 (m, 1 H, CHH), 3.63C3.56 (m, 1H, CHH), 2.31C2.24 (m, 1H, CHH), 2.16C2.09 (m, 1H, CHH), 2.10C2.04 (m, 1H, CHH), 2.02C1.91 (m, 4H, CH2), 0.98 (t, 3H, = 7.4 Hz, CH3), 0.96 (d, 6H, = 2.1 Hz, 2 CH3); 13C-NMR (150 MHz, CDCl3).DMSO (1%, v/v) was used as the bad control. of fresh c-Met inhibitors. Herein we wish to record our attempts in this respect (Shape SCR7 pyrazine 2). Open up in another window Shape 2 Scaffolds useful for the structural marketing predicated on BMS-777607 with this paper. 2. Discussion and Results 2.1. Chemistry As demonstrated in Structure 1, saponification of isobutyl ester 2 with lithium hydroxide offered the piperidinone 3-carboxylic acidity 3, that could become further brominated providing substance 4 in 92% produce. Alternatively, deprotonation of substance 2 with sodium hydride, accompanied by treatment with an alkyl halide (MeI, EtBr, or IC50 (M)IC50 (M)(2). 1-Fluoro-4-iodobenzene (2.22 g, 10 mmol) and piperidin-2-one (1.2 g, 12 mmol) had been added to dried out DMF (30 mL), accompanied by the addition of K3PO4 (6.36 g, 30 mmol) and CuI (190 mg, 0.1 mmol). The blend was warmed to 100 C for 12 h before filtering through Celite. After cleaning with ethyl acetate (3 10 mL), the mixed organic stage was concentrated as well as the residue was purified by column chromatography to provide 1-(4-fluorophenyl)piperidin-2-one (1.73 g, 90%) like a yellowish solid. This = 10.6, 6.7 Hz, CH), 3.83 (d, 1 H, = 6.7 Hz, CHH), 3.70C3.61 (m, 1H, CHH), 3.58 (t, 1 H, = 6.9 Hz, CH), 2.32C2.24 (m, 1H, CHH), 2.23C2.16 (m, 1H, CHH), 2.12C2.04 (m, 1H, CHH), 2.02C1.87 (m, 2H, CH, CHH), 0.94 (d, 6 H, = 6.6 Hz, CH3); 13C-NMR (150 MHz, CDCl3) 171.0, 166.3, 162.1, 160.4, 138.8, 127.9, 116.2, 100.0, 71.5, 51.6, 49.6, 27.8, 25.3, 21.4, 19.1; HR-MS (ESI) Calcd for C16H21FNO3 [M + H]+ 294.1506, Found out 294.1518. (3). To a remedy of 2 (217 mg, 0.74 mmol) in THF/MeOH/H2O (1/1/1, 3 mL altogether) in 0 C was added LiOH monohydrate (94 mg, 2.2 mmol). The response blend was warmed to space temp and stirred for 5 h. The perfect solution is was acidified to pH 1 with 1 mol/L HCl and extracted with EtOAc (3 20 mL). The organic components had been combined and cleaned with brine (2 5 mL). Evaporation from the solvent offered the corresponding acidity 3 (152 mg, 87%) like a white solid. 1H-NMR (600 MHz, CDCl3) 7.33C7.28 (m, 1H, ArH), 7.25C7.19 (m, 1H, ArH), 3.69C3.55 (m, 2H, NCH2), 3.43 (dd, 1H, = 8.2, 6.5 Hz, CH), 2.16C2.10 (m, 1 H, CHH), 2.08C2.02 (m, 1H, CHH), 1.98C1.91 (m, 1H, CHH), 1.91C1.83 (m, 1H, CHH); 13C-NMR (150 MHz, CDCl3) 174.3, 170.2, 161.3, 159.6, 138.7, 127.9, 115.6, 51.8, 50.3, 27.5, 21.6; HR-MS (ESI) Calcd for C12H13FNO3 238.0880 [M + H]+, found 238.0910. (4). To a remedy of acidity 3 (220 mg, 0.93 mmol) in Et2O (5 mL) was added liquid Br2 (48 L, 0.93 mmol) at 0 C. The response blend was stirred for 2 h before focused = 12.1, 4.6 Hz, NCHH), 3.82 (ddt, 1H, = 13.0, 6.3, 2.4 Hz, NCHH), 2.77C2.69 (m, 1H, CH(5a). 87% produce; 1H-NMR (600 MHz, CDCl3) 7.25C7.19 (m, 1 H, ArH), 7.12C7.01 (m, 1H, ArH), 4.06C3.88 (m, 2H, OCH2), 3.78C3.58 (m, 1H, CH= 2.4 Hz, CH3), 0.97 (d, 3H, = 2.0 HzCH3), 0.96 (d, 3H, = 2.1 Hz, CH3); 13C-NMR (150 MHz, CDCl3) 173.8, 170.1, 161.9, 160.2, 139.3, 127.8, 116.0, 115.9, 71.5, 51.9, 51.3, 33.6, 27.8, 22.9, 20.4, 19.2; HR-MS (ESI) Calcd for C17H23FNO3 308.1662 [M + H]+, found 308.1599. (5b). 76% produce; 1H-NMR (600 MHz, CDCl3) 7.24C7.18 (m, 2H, ArH), 7.08C7.03 (m, 2H, ArH), 4.01C3.90 (m, 2H, OCH2), 3.72C3.65 (m, 1 H, CHH), 3.63C3.56 (m, 1H, CHH), 2.31C2.24 (m, 1H, CHH), 2.16C2.09 (m, 1H, CHH), 2.10C2.04 (m, 1H, CHH), 2.02C1.91 (m, 4H, CH2), 0.98 (t, 3H, = 7.4 Hz, CH3), 0.96 (d, 6H, = 2.1 Hz, 2 CH3); 13C-NMR (150 MHz, CDCl3) 173.6, 170.0, 161.8, 160.2, 139.3, 127.8, 116.0, 71.5, 51.9, 51.3, 33.6, 30.1, 27.8, 22.9, 20.4, 19.8; HR-MS (ESI) Calcd for C18H25FNO3 322.1819 [M + H]+, found 322.1830. (5c). 83% produce; 1H-NMR (600 MHz, CDCl3) 7.23C7.18 (m, 2H, ArH), 7.08C7.02 (m, 2H, ArH), 4.00C3.89 (m, 2H, OCH2), 3.72C3.66 (m, 1H, CHH), 3.61C3.56 (m, 1H, CHH), 2.32C2.26 (m, 1H, CHH), 2.10C1.86 (m, 6H), 1.46C1.38 (m, 1H, CHH), 1.37C1.29 (m, 2H, CH2), 1.30C1.21 (m, 1H, CHH), 0.96 (d, 6H, = 2.1 Hz, 2 CH3), 0.90 (t, 3H, = 7.2 Hz, CH3); 13C-NMR (150 MHz, CDCl3) 173.5, 169.4, 161.8, 160.2, 139.4, 127.8, 115.9, 71.5, 54.9, 51.6, 35.7, 30.1, 27.0, 23.2, 20.7, 19.2,.1H-NMR (600 MHz, CDCl3) 8.06 (br s, 1H, ArH), 7.12 (br s, 2H, ArH), 6.92 (t, 1H, = 8.6 Hz, ArH), 6.80 (d, 2H, = 8.2 Hz, ArH), 6.47 (dd, 1H, = 11.8, 2.7 Hz, ArH), 6.45C6.39 (m, 1H, ArH), 6.15 (d, 1H, = 5.8 Hz, ArH), 4.36 (br s, 2H, NH2), 3.92 (br s, 2H, CH2), 3.78 (s, 3H, CH3). (14). in 92% produce. Alternatively, deprotonation of substance 2 with sodium hydride, accompanied by treatment with an alkyl halide (MeI, EtBr, or IC50 (M)IC50 (M)(2). 1-Fluoro-4-iodobenzene (2.22 g, 10 mmol) and piperidin-2-one (1.2 g, 12 mmol) had been added to dried out DMF (30 mL), accompanied by the addition of K3PO4 (6.36 g, 30 mmol) and CuI (190 mg, 0.1 mmol). The blend was warmed to 100 C for 12 h before filtering through Celite. After cleaning with ethyl acetate (3 10 mL), the mixed organic stage was concentrated as well as the residue was purified by column chromatography to provide 1-(4-fluorophenyl)piperidin-2-one (1.73 g, 90%) like a yellowish solid. This = 10.6, 6.7 Hz, CH), 3.83 (d, 1 H, = 6.7 Hz, CHH), 3.70C3.61 (m, 1H, CHH), 3.58 (t, 1 H, = 6.9 Hz, CH), 2.32C2.24 (m, 1H, CHH), 2.23C2.16 (m, 1H, CHH), 2.12C2.04 (m, 1H, CHH), 2.02C1.87 (m, 2H, CH, CHH), 0.94 (d, 6 H, = 6.6 Hz, CH3); 13C-NMR (150 MHz, CDCl3) 171.0, 166.3, 162.1, 160.4, 138.8, 127.9, 116.2, 100.0, 71.5, 51.6, 49.6, 27.8, 25.3, 21.4, 19.1; HR-MS (ESI) Calcd for C16H21FNO3 [M + H]+ 294.1506, Found out 294.1518. (3). To a remedy of 2 (217 mg, 0.74 mmol) in THF/MeOH/H2O (1/1/1, 3 mL altogether) in 0 C was added LiOH monohydrate (94 mg, 2.2 mmol). The response blend was warmed to space temp and stirred for 5 h. The perfect solution is was acidified to pH 1 with 1 mol/L HCl and extracted with EtOAc (3 20 mL). The organic components had been combined and cleaned with brine (2 5 mL). Evaporation from the solvent offered the corresponding acidity 3 (152 mg, 87%) like a white solid. 1H-NMR (600 MHz, CDCl3) 7.33C7.28 (m, 1H, ArH), 7.25C7.19 (m, 1H, ArH), 3.69C3.55 (m, 2H, NCH2), 3.43 (dd, 1H, = 8.2, 6.5 Hz, CH), 2.16C2.10 (m, 1 H, CHH), 2.08C2.02 (m, 1H, CHH), 1.98C1.91 (m, 1H, CHH), 1.91C1.83 (m, 1H, CHH); 13C-NMR (150 MHz, CDCl3) 174.3, 170.2, 161.3, 159.6, 138.7, 127.9, 115.6, 51.8, 50.3, 27.5, 21.6; HR-MS (ESI) Calcd for C12H13FNO3 238.0880 [M + H]+, found 238.0910. (4). To a remedy of acidity 3 (220 mg, 0.93 mmol) in Et2O (5 mL) was added liquid Br2 (48 L, 0.93 mmol) at 0 C. The response blend was stirred for 2 h before focused = 12.1, 4.6 Hz, NCHH), 3.82 (ddt, 1H, = 13.0, 6.3, 2.4 Hz, NCHH), 2.77C2.69 (m, 1H, CH(5a). 87% produce; 1H-NMR (600 MHz, CDCl3) 7.25C7.19 (m, 1 H, ArH), 7.12C7.01 (m, 1H, ArH), 4.06C3.88 (m, 2H, OCH2), 3.78C3.58 (m, 1H, CH= 2.4 Hz, CH3), 0.97 (d, 3H, = 2.0 HzCH3), 0.96 (d, 3H, = 2.1 Hz, CH3); 13C-NMR (150 MHz, CDCl3) 173.8, 170.1, 161.9, 160.2, 139.3, 127.8, 116.0, 115.9, 71.5, 51.9, 51.3, 33.6, 27.8, 22.9, 20.4, 19.2; HR-MS (ESI) Calcd for C17H23FNO3 308.1662 [M + H]+, found 308.1599. (5b). 76% produce; 1H-NMR (600 MHz, CDCl3) 7.24C7.18 (m, 2H, ArH), 7.08C7.03 (m, 2H, ArH), 4.01C3.90 (m, 2H, OCH2), 3.72C3.65 (m, 1 H, CHH), 3.63C3.56 (m, 1H, CHH), 2.31C2.24 (m, 1H, CHH), 2.16C2.09 (m, 1H, CHH), 2.10C2.04 (m, 1H, CHH), 2.02C1.91 (m, 4H, CH2), 0.98 (t, 3H, = 7.4 Hz, CH3), 0.96 (d, 6H, = 2.1 Hz, 2 CH3); 13C-NMR (150 MHz, CDCl3) 173.6, 170.0, 161.8, 160.2, 139.3, 127.8, 116.0, 71.5, 51.9, 51.3, 33.6, 30.1, 27.8, 22.9, 20.4, 19.8; HR-MS (ESI) Calcd for C18H25FNO3 322.1819 [M + H]+, found 322.1830. (5c). 83% produce; 1H-NMR (600 MHz, CDCl3) 7.23C7.18 (m, 2H, ArH), 7.08C7.02 (m, 2H, ArH), 4.00C3.89 (m, 2H, OCH2), 3.72C3.66 (m, 1H, CHH), 3.61C3.56 (m, 1H, CHH), 2.32C2.26 (m, 1H, CHH), 2.10C1.86 (m, 6H), 1.46C1.38 (m, 1H, CHH), 1.37C1.29 (m, 2H, CH2), 1.30C1.21 (m, 1H, CHH), 0.96 (d, 6H, = 2.1 Hz, 2 CH3), 0.90 (t,.A 100-L aliquot of a remedy containing 0.03% H2O2 and 2 mg/ml o-phenylenediamine in 0.1 mol/L citrate buffer (pH 5.5) was added. marketing predicated on BMS-777607 with this paper. 2. Outcomes and Dialogue 2.1. Chemistry As demonstrated in Structure 1, saponification of isobutyl ester 2 with lithium hydroxide offered the piperidinone 3-carboxylic acidity 3, that could become further brominated providing substance 4 in 92% produce. Alternatively, deprotonation of compound 2 with sodium hydride, SCR7 pyrazine followed by treatment with an alkyl halide (MeI, EtBr, or IC50 (M)IC50 (M)(2). 1-Fluoro-4-iodobenzene (2.22 g, 10 mmol) and piperidin-2-one (1.2 g, 12 mmol) were added to dry DMF (30 mL), followed by the addition of K3PO4 (6.36 g, 30 mmol) and CuI (190 mg, 0.1 mmol). The combination was heated to 100 C for 12 h before filtering through Celite. After washing with ethyl acetate (3 10 mL), the combined organic phase was concentrated and the residue was purified by column chromatography to give 1-(4-fluorophenyl)piperidin-2-one (1.73 g, 90%) like a yellow solid. This = 10.6, 6.7 Hz, CH), 3.83 (d, 1 H, = 6.7 Hz, CHH), 3.70C3.61 (m, 1H, CHH), 3.58 (t, 1 H, = 6.9 Hz, CH), 2.32C2.24 (m, 1H, CHH), 2.23C2.16 (m, 1H, CHH), 2.12C2.04 (m, 1H, CHH), 2.02C1.87 (m, 2H, CH, CHH), 0.94 (d, 6 H, = 6.6 Hz, CH3); 13C-NMR (150 MHz, CDCl3) 171.0, 166.3, 162.1, 160.4, 138.8, 127.9, 116.2, 100.0, 71.5, 51.6, 49.6, 27.8, 25.3, 21.4, 19.1; HR-MS (ESI) Calcd for C16H21FNO3 [M + H]+ 294.1506, Found out 294.1518. (3). To a solution of 2 (217 mg, 0.74 mmol) in THF/MeOH/H2O (1/1/1, 3 mL in total) at 0 C was added LiOH monohydrate (94 mg, 2.2 mmol). The reaction combination was warmed to space heat and stirred for 5 h. The perfect solution is was acidified to pH 1 with 1 mol/L HCl and extracted with EtOAc (3 20 mL). The organic components were combined and washed with brine (2 5 mL). Evaporation of the solvent offered the corresponding acidity 3 (152 mg, 87%) like a white solid. 1H-NMR (600 MHz, CDCl3) 7.33C7.28 (m, 1H, ArH), 7.25C7.19 (m, 1H, ArH), 3.69C3.55 (m, 2H, NCH2), 3.43 (dd, 1H, = 8.2, 6.5 Hz, CH), 2.16C2.10 (m, 1 H, CHH), 2.08C2.02 (m, 1H, CHH), 1.98C1.91 (m, 1H, CHH), 1.91C1.83 (m, 1H, CHH); 13C-NMR (150 MHz, CDCl3) 174.3, 170.2, 161.3, 159.6, 138.7, 127.9, 115.6, 51.8, 50.3, 27.5, 21.6; HR-MS (ESI) Calcd for C12H13FNO3 238.0880 [M + H]+, found 238.0910. (4). To a solution of acid 3 (220 mg, 0.93 mmol) in Et2O (5 mL) was added liquid Br2 (48 L, 0.93 mmol) at 0 C. The reaction combination was stirred for 2 h before concentrated = 12.1, 4.6 Hz, NCHH), 3.82 (ddt, 1H, = 13.0, 6.3, 2.4 Hz, NCHH), 2.77C2.69 (m, 1H, CH(5a). 87% yield; 1H-NMR (600 MHz, CDCl3) 7.25C7.19 (m, 1 H, ArH), 7.12C7.01 (m, 1H, ArH), 4.06C3.88 (m, 2H, OCH2), 3.78C3.58 (m, 1H, CH= 2.4 Hz, CH3), 0.97 (d, 3H, = 2.0 HzCH3), 0.96 (d, 3H, = 2.1 Hz, CH3); 13C-NMR (150 MHz, CDCl3) 173.8, 170.1, 161.9, 160.2, 139.3, 127.8, 116.0, 115.9, 71.5, 51.9, 51.3, 33.6, 27.8, 22.9, 20.4, 19.2; HR-MS (ESI) Calcd for C17H23FNO3 308.1662 [M + H]+, found 308.1599. (5b). 76% yield; 1H-NMR (600 MHz, CDCl3) 7.24C7.18 (m, 2H, ArH), 7.08C7.03 (m, 2H, ArH), 4.01C3.90 (m, 2H, OCH2), 3.72C3.65 (m, 1 H, CHH), 3.63C3.56 (m, 1H, CHH), 2.31C2.24 (m, 1H, CHH), 2.16C2.09 (m, 1H, CHH), 2.10C2.04 (m, 1H, CHH), 2.02C1.91 (m, 4H, CH2), 0.98 (t, 3H, = 7.4 Hz, CH3), 0.96 (d, 6H, = 2.1 Hz, 2 CH3); 13C-NMR (150 MHz, CDCl3) 173.6, 170.0, 161.8, 160.2, 139.3, 127.8, 116.0, 71.5, 51.9, 51.3, 33.6, 30.1, 27.8, 22.9, 20.4, 19.8; HR-MS (ESI) Calcd for C18H25FNO3 322.1819 [M + H]+, found 322.1830. (5c). 83% yield; 1H-NMR (600 MHz, CDCl3) 7.23C7.18 (m, 2H, ArH), 7.08C7.02 (m, 2H, ArH), 4.00C3.89.A 50-L aliquot of 10 mol/L ATP solution diluted in kinase reaction buffer (50 mmol/L HEPES [pH 7.4], 50 mmol/L MgCl2, 0.5 mmol/L MnCl2, 0.2 mmol/L Na3VO4, and 1 mmol/L DTT) was added to each well; 1 L of various concentrations of indicated compound diluted in 1% DMSO (v/v) (Sigma) were then added to each reaction well. compound 4 in 92% yield. On the other hand, deprotonation of compound 2 with sodium hydride, followed by treatment with an alkyl halide (MeI, EtBr, or IC50 (M)IC50 (M)(2). 1-Fluoro-4-iodobenzene (2.22 g, 10 mmol) and piperidin-2-one (1.2 g, 12 mmol) were added to dry DMF (30 mL), followed by the addition of K3PO4 (6.36 g, 30 mmol) and CuI (190 mg, 0.1 mmol). The combination was heated to 100 C for 12 h before filtering through Celite. After washing with ethyl acetate (3 10 mL), the combined organic phase was concentrated and the residue was purified by column chromatography to give 1-(4-fluorophenyl)piperidin-2-one (1.73 g, 90%) like a yellow solid. This = 10.6, 6.7 Hz, CH), 3.83 (d, 1 H, = 6.7 Hz, CHH), 3.70C3.61 (m, 1H, CHH), 3.58 (t, 1 H, = 6.9 Hz, CH), 2.32C2.24 (m, 1H, CHH), 2.23C2.16 (m, 1H, CHH), 2.12C2.04 (m, 1H, CHH), 2.02C1.87 (m, 2H, CH, CHH), 0.94 (d, 6 H, = 6.6 Hz, CH3); 13C-NMR (150 MHz, CDCl3) 171.0, 166.3, 162.1, 160.4, 138.8, 127.9, 116.2, 100.0, 71.5, 51.6, 49.6, 27.8, 25.3, 21.4, 19.1; HR-MS (ESI) Calcd for C16H21FNO3 [M + H]+ 294.1506, Found out 294.1518. (3). To a solution of 2 (217 mg, 0.74 mmol) in THF/MeOH/H2O (1/1/1, SCR7 pyrazine 3 mL in total) at 0 C was added LiOH monohydrate (94 mg, 2.2 mmol). The reaction combination was warmed to space heat and stirred for 5 Gpc3 h. The perfect solution is was acidified to pH 1 with 1 mol/L HCl and extracted with EtOAc (3 20 mL). The organic components were combined and washed with brine (2 5 mL). Evaporation of the solvent offered the corresponding acidity 3 (152 mg, 87%) like a white solid. 1H-NMR (600 MHz, CDCl3) 7.33C7.28 (m, 1H, ArH), 7.25C7.19 (m, 1H, ArH), 3.69C3.55 (m, 2H, NCH2), 3.43 (dd, 1H, = 8.2, 6.5 Hz, CH), 2.16C2.10 (m, 1 H, CHH), 2.08C2.02 (m, 1H, CHH), 1.98C1.91 (m, 1H, CHH), 1.91C1.83 (m, 1H, CHH); 13C-NMR (150 MHz, CDCl3) 174.3, 170.2, 161.3, 159.6, 138.7, 127.9, 115.6, 51.8, 50.3, 27.5, 21.6; HR-MS (ESI) Calcd for C12H13FNO3 238.0880 [M + H]+, found 238.0910. (4). To a solution of acid 3 (220 mg, 0.93 mmol) in Et2O (5 mL) was added liquid Br2 (48 L, 0.93 mmol) at 0 C. The reaction combination was stirred for 2 h before concentrated = 12.1, 4.6 Hz, NCHH), 3.82 (ddt, 1H, = 13.0, 6.3, 2.4 Hz, NCHH), 2.77C2.69 (m, 1H, CH(5a). 87% yield; 1H-NMR (600 MHz, CDCl3) 7.25C7.19 (m, 1 H, ArH), 7.12C7.01 (m, 1H, ArH), 4.06C3.88 (m, 2H, OCH2), 3.78C3.58 (m, 1H, CH= 2.4 Hz, CH3), 0.97 (d, 3H, = 2.0 HzCH3), 0.96 (d, 3H, = 2.1 Hz, CH3); 13C-NMR (150 MHz, CDCl3) 173.8, 170.1, 161.9, 160.2, 139.3, 127.8, 116.0, 115.9, 71.5, 51.9, 51.3, 33.6, 27.8, 22.9, 20.4, 19.2; HR-MS (ESI) Calcd for C17H23FNO3 308.1662 [M + H]+, found 308.1599. (5b). 76% yield; 1H-NMR (600 MHz, CDCl3) 7.24C7.18 (m, 2H, ArH), 7.08C7.03 (m, 2H, ArH), 4.01C3.90 (m, 2H, OCH2), 3.72C3.65 (m, 1 H, CHH), 3.63C3.56 (m, 1H, CHH), 2.31C2.24 (m, 1H, CHH), 2.16C2.09 (m, 1H, CHH), 2.10C2.04 (m, 1H, CHH), 2.02C1.91 (m, 4H, CH2), 0.98 (t, 3H, = 7.4 Hz, CH3), 0.96 (d, 6H, = 2.1 Hz, 2 CH3); 13C-NMR (150 MHz, CDCl3) 173.6, 170.0, 161.8, 160.2, 139.3, 127.8, 116.0, 71.5, 51.9, 51.3, 33.6, 30.1, 27.8, 22.9, 20.4, 19.8; HR-MS (ESI) Calcd for C18H25FNO3 322.1819 [M + H]+, found 322.1830. (5c). 83% yield;.