2091328-57-1

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: To a solution of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one (200 mg, 0.45 mmol) (prepared according to WO 02/48115, example 2D) in tetrahydrofurane (4 ml), is added 2-aminomethyloxetane (the product of step 2) (79 mg, 0.91 mmol), and the mixture is heated to reflux for 30 minutes. The solution is allowed to cool to ambient temperature and the solvent evaporated in vacuo. The residue is purified by prep. HPLC (hexane/ethyl acetate gradient on LiChrospher Si 60, Merck NW25 column) to afford 180 mg (71%) of the title compound as a white solid. [1H-NMR (CDCl3): 10.21 (s, 1H), 8.48 (d, 1H), 7.88 (d, 1H), 7.41 (m, 1H), 7.32 (s, 1H), 7.29 (m, 2H), 6.63 (m, 1H), 4.98 (m, 1H), 4.68 (m, 1H), 4.48 (m, 1H), 3.71 (m, 1H), 3.59 (m, 1H), 2.68 (m, 1H), 2.43 (m, 1H), 2.19 (s, 3H); MS (electrospray ES+): 528, 530 ((M+H)+)]. the mixture is heated to reflux for 30 minutes the solvent evaporated in vacuo The residue is purified by prep

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

実験手順: A mixture of 6-({3-(aminocarbonyl)-5-[2-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-thienyl}amino)pyridine-2-carboxylic acid (Table 3, Example 40) (50 mg, 0.12 mmol), 1-oxetan-2-ylmethanamine (11 mg, 0.12 mmol), 1-hydroxybenzotriazole hydrate (22 mg, 0.14 mmol), and PS-Carbodiimide (240 mg, 0.30 mmol, 1.25 mmol/g) in DMF (4 mL) was irradiated in a microwave at 100° C. for 10 minutes. Upon completion, the crude reaction was filtered, concentrated, and purified by silica gel chromatography (0-7% methanol/ethyl acetate) to afford the title compound. was irradiated in a microwave at 100° C. for 10 minutes Upon completion, the crude reaction was filtered concentrated purified by silica gel chromatography (0-7% methanol/ethyl acetate)

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: To a solution of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one (200 mg, 0.45 mmol) (prepared according to WO 02/48115, example 2D) in tetrahydrofurane (4 ml), is added 2-aminomethyloxetane (the product of step 2) (79 mg, 0.91 mmol), and the mixture is heated to reflux for 30 minutes. The solution is allowed to cool to ambient temperature and the solvent evaporated in vacuo. The residue is purified by prep. HPLC (hexane/ethyl acetate gradient on LiChrospher Si 60, Merck NW25 column) to afford 180 mg (71%) of the title compound as a white solid. [1H-NMR (CDCl3): 10.21 (s, 1H), 8.48 (d, 1H), 7.88 (d, 1H), 7.41 (m, 1H), 7.32 (s, 1H), 7.29 (m, 2H), 6.63 (m, 1H), 4.98 (m, 1H), 4.68 (m, 1H), 4.48 (m, 1H), 3.71 (m, 1H), 3.59 (m, 1H), 2.68 (m, 1H), 2.43 (m, 1H), 2.19 (s, 3H); MS (electrospray ES+): 528, 530 ((M+H)+)]. the mixture is heated to reflux for 30 minutes the solvent evaporated in vacuo The residue is purified by prep

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

実験手順: A mixture of 6-({3-(aminocarbonyl)-5-[2-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-thienyl}amino)pyridine-2-carboxylic acid (Table 3, Example 40) (50 mg, 0.12 mmol), 1-oxetan-2-ylmethanamine (11 mg, 0.12 mmol), 1-hydroxybenzotriazole hydrate (22 mg, 0.14 mmol), and PS-Carbodiimide (240 mg, 0.30 mmol, 1.25 mmol/g) in DMF (4 mL) was irradiated in a microwave at 100° C. for 10 minutes. Upon completion, the crude reaction was filtered, concentrated, and purified by silica gel chromatography (0-7% methanol/ethyl acetate) to afford the title compound. was irradiated in a microwave at 100° C. for 10 minutes Upon completion, the crude reaction was filtered concentrated purified by silica gel chromatography (0-7% methanol/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 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one (200 mg, 0.45 mmol) (prepared according to WO 02/48115, example 2D) in tetrahydrofurane (4 ml), is added 2-aminomethyloxetane (the product of step 2) (79 mg, 0.91 mmol), and the mixture is heated to reflux for 30 minutes. The solution is allowed to cool to ambient temperature and the solvent evaporated in vacuo. The residue is purified by prep. HPLC (hexane/ethyl acetate gradient on LiChrospher Si 60, Merck NW25 column) to afford 180 mg (71%) of the title compound as a white solid. [1H-NMR (CDCl3): 10.21 (s, 1H), 8.48 (d, 1H), 7.88 (d, 1H), 7.41 (m, 1H), 7.32 (s, 1H), 7.29 (m, 2H), 6.63 (m, 1H), 4.98 (m, 1H), 4.68 (m, 1H), 4.48 (m, 1H), 3.71 (m, 1H), 3.59 (m, 1H), 2.68 (m, 1H), 2.43 (m, 1H), 2.19 (s, 3H); MS (electrospray ES+): 528, 530 ((M+H)+)]. the mixture is heated to reflux for 30 minutes the solvent evaporated in vacuo The residue is purified by prep

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

実験手順: A mixture of 6-({3-(aminocarbonyl)-5-[2-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-thienyl}amino)pyridine-2-carboxylic acid (Table 3, Example 40) (50 mg, 0.12 mmol), 1-oxetan-2-ylmethanamine (11 mg, 0.12 mmol), 1-hydroxybenzotriazole hydrate (22 mg, 0.14 mmol), and PS-Carbodiimide (240 mg, 0.30 mmol, 1.25 mmol/g) in DMF (4 mL) was irradiated in a microwave at 100° C. for 10 minutes. Upon completion, the crude reaction was filtered, concentrated, and purified by silica gel chromatography (0-7% methanol/ethyl acetate) to afford the title compound. was irradiated in a microwave at 100° C. for 10 minutes Upon completion, the crude reaction was filtered concentrated purified by silica gel chromatography (0-7% methanol/ethyl acetate)