formohydrazide

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:

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:

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: 1-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclopropanecarboxylic acid (TFA salt, 110 mg, 0.206 mmol), formic acid hydrazide (37 mg, 0.617 mmol), HOBT (95 mg, 0.617 mmol), and EDC (118 mg, 0.617 mmol) were combined with DMF (5 mL) and DIEA (80 mg, 0.617 mmol). The reaction was stirred for 3 h at room temperature. It was subsequently diluted with water and extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. The residue was triturated with ether and filtered to provide N′-formyl-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclopropanecarbohydrazide (88 mg, 92%) as a colorless solid. MS ESI: [M+H]+ m/z 463.0. extracted with ethyl acetate (2×) The combined organic layers were washed with brine dried (MgSO4) filtered evaporated The residue was triturated with ether filtered

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

実験手順: The product from Step 1 (HCl salt, 187 mg, 0.408 mmol), HOBT (125 mg, 0.815 mmol), and EDC (156 mg, 0.815 mmol) were combined with dioxane (5 mL) and stirred for 5 min at room temperature. Formic acid hydrazide (73 mg, 1.223 mmol) and DIEA (105 mg, 0.815 mmol) were subsequently added. The reaction was stirred overnight at room temperature. The reaction was diluted with water and extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. Column chromatography on silica (50-100% EtOAc/hexanes) afforded N′-formyl-2-methyl-2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propanehydrazide (87 mg, 46%) as a colorless solid. MS ESI: [M+H]+ m/z 465.0. The reaction was stirred overnight at room temperature extracted with ethyl acetate (2×) The combined organic layers were washed with brine dried (Na2SO4) filtered evaporated