丙酸肼

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.250 g, 0.905 mmol) in DCM (15.0 mL) were added propanehydrazide 202 (0.120 g, 1.358 mmol), 1-hydroxybenzotriazole (0.186 g, 1.358 mmol) and 1-ethyl-(3-dimethylamino propyl) carbodiimide hydrochloride (0.260 g, 1.358 mmol) sequentially at room temperature. The mixture was stirred at room temperature overnight, diluted with DCM and concentrated to provide a residue which was subjected to chromatography to give 203 (0.31 g, 99%) as a white foam. concentrated to provide a residue which

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 7.6 g. of 3-chloro-6-phenylpyridazine, 7.4 g. of propionic acid hydrazide and 60 ml of n-butanol is stirred at reflux temperature for 48 hours. The solution is cooled in a chilled room, concentrated to remove the solvent and triturated with water giving crystals. The mixture is filtered, washed with petroleum ether and water and dried. The product is recrystallized from 20 ml. of ethanol giving 3-ethyl-6-phenyl-1,2,4-triazolo[4,3-b]pyridazine, m.p. 133°-135° C. A mixture of 7.6 g at reflux temperature for 48 hours The solution is cooled in a chilled room concentrated to remove the solvent triturated with water giving crystals The mixture is filtered washed with petroleum ether and water dried The product is recrystallized from 20 ml

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 7.6 g. of 3-chloro-6-phenylpyridazine, 7.4 g. of propionic acid hydrazide and 60 ml of n-butanol is stirred at reflux temperature for 48 hours. The solution is cooled in a chilled room, concentrated to remove the solvent and triturated with water giving crystals. The mixture is filtered, washed with petroleum ether and water and dried. The product is recrystallized from 20 ml. of ethanol giving 3-ethyl-6-phenyl-1,2,4-triazolo[4,3-b]pyridazine, m.p. 133°-135° C. A mixture of 7.6 g at reflux temperature for 48 hours The solution is cooled in a chilled room concentrated to remove the solvent triturated with water giving crystals The mixture is filtered washed with petroleum ether and water dried The product is recrystallized from 20 ml

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The general procedure of Example 4 is repeated but replacing the 3-benzoyl-2,3-dimethyl-propionic acid and N-acetylhydrazine employed in that example with 3-benzoyl-3-methyl-propionic acid and N-propionylhydrazine.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 6.11 gm (0.05 mole) of 2-acetylpyrazine, 4.41 gm (0.05 mole) of propanoic acid hydrazide and 100 ml of absolute ethanol is refluxed 10 hr. The mixture is cooled. The white crystals which deposit are collected and dried to yield 6.17 gm (64%) of the title compound having a melting point of 181.3° C. is refluxed 10 hr The mixture is cooled The white crystals which deposit are collected dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 6.11 gm (0.05 mole) of 2-acetylpyrazine, 4.41 gm (0.05 mole) of propanoic acid hydrazide and 100 ml of absolute ethanol is refluxed 10 hr. The mixture is cooled. The white crystals which deposit are collected and dried to yield 6.17 gm (64%) of the title compound having a melting point of 181.3° C. is refluxed 10 hr The mixture is cooled The white crystals which deposit are collected dried

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of the carboxylic acid of Example 9 or 16 (6b, 354 mg, 1.28 mmol) in tetrahydrofuran (10 mL) were added triethylamine (0.216 mL) and isobutyl chloroformate (208 μl) under ice-cooling, followed by agitating at 0° C. for 15 minutes. To the reaction solution were added a solution of propionohydrazide (161 mg, prepared following a procedure analogous to Reference Example 3 and Reference Example 6) in tetrahydrofuran (3 mL) at 0° C., followed by stirring at room temperature for 1 hour, and then concentrating under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1-0/1) to afford 425 mg of the title compound (yield 96%). cooling prepared at 0° C. by stirring at room temperature for 1 hour concentrating under reduced pressure The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1-0/1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was synthesized using standard chemical manipulations and procedures similar to those used for the preparation of compound 152.8 using 4-fluoro-2-methylbenzoic acid instead of 4-bromo-2-methylbenzoic acid and propionohydrazide instead of acetohydrazide.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was synthesized using standard chemical manipulations and procedures similar to those used for the preparation of compound 152.8 using 4-fluoro-2-methylbenzoic acid instead of 4-bromo-2-methylbenzoic acid and propionohydrazide instead of acetohydrazide.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared using standard chemical manipulations and procedures similar to those used for the preparation of compound 152 and using propionohydrazide instead of acetohydrazide. m/z (ES+) 454 (M+H)+. 1H NMR (400 MHz, Chloroform-d) δ 7.75-7.43 (m, 3H), 7.40-7.17 (m, 3H), 5.18-4.81 (m, 1H), 4.30-3.91 (m, 1H), 3.84-3.55 (m, 1H), 3.21-2.99 (m, 1H), 2.92-2.69 (m, 4H), 2.40 and 2.32 (2 singlets, amide rotamers, ArCH3, 3H), 2.25-1.84 (m, 7H), 1.83-1.42 (m, 3H), 1.32 (t, 3H).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared using standard chemical manipulations and procedures similar to those used for the preparation of compound 152 and using propionohydrazide instead of acetohydrazide. m/z (ES+) 454 (M+H)+. 1H NMR (400 MHz, Chloroform-d) δ 7.75-7.43 (m, 3H), 7.40-7.17 (m, 3H), 5.18-4.81 (m, 1H), 4.30-3.91 (m, 1H), 3.84-3.55 (m, 1H), 3.21-2.99 (m, 1H), 2.92-2.69 (m, 4H), 2.40 and 2.32 (2 singlets, amide rotamers, ArCH3, 3H), 2.25-1.84 (m, 7H), 1.83-1.42 (m, 3H), 1.32 (t, 3H).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound (28.5 mg, 74%) was synthesized from 1-[3-(7-fluoro-quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyrazin-5-yl]-ethanone (30.0 mg, 0.09 mmol) and propionic acid hydrazide (24.6 mg, 0.28 mmol) using the same procedure as described in the synthesis of example 72. 1H-NMR (400 MHz, DMSO-d6) δ ppm 10.93, 10.76 (bs, 1H), 9.45 (s, 1H), 8.92 (dd, 1H), 8.41 (d, 1H), 8.18 (d, 1H), 7.83 (d, 1H), 7.53 (dd, 1H), 6.22 (s, 2H), 2.79 (q, 2H), 2.31 (s, 3H), 1.09 (t, 3H). LCMS (method E): [MH]+=393, tR=4.78 min. as described in the synthesis of example 72