تفاعل #68665

معادلة التفاعل

NaHCO3

methyl 2,2-difluoro-2-(quinolin-6-yl)acetate

1-(6-(3-methylisothiazol-5-yl)pyridazin-3-yl)hydrazine

p-toluenesulfonic acid monohydrate

→

6-(difluoro(6-(3-methylisothiazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)quinoline

المذيبات

EtOAc

dioxane

ظروف التفاعل

المعالجة

1. 1
   أخرىThe organic phase was separated
2. 2
   غسيلwashed with 40 mL of brine
3. 3
   تجفيفdried over Na2SO4
4. 4
   تركيزconcentrated in vacuo
5. 5
   أخرىThe residue was purified by a silica gel column chromatography (EtOAc to 10% MeOH/EtOAc)
6. 6
   أخرىto give yellow glass
7. 7
   أخرىThe product was further purified by a prep-HPLC
8. 8
   أخرىto give yellow glass

الإجراء التجريبي

A mixture of methyl 2,2-difluoro-2-(quinolin-6-yl)acetate (0.50 g, 2.1 mmol), 1-(6-(3-methylisothiazol-5-yl)pyridazin-3-yl)hydrazine (0.25 g, 1.2 mmol) and p-toluenesulfonic acid monohydrate (0.40 g, 2.1 mmol) in 5 mL of dioxane was heated at 150° C. for 1 hour in a microwave. The mixture was then diluted with 70 mL of EtOAc and 40 mL of satd. NaHCO3 solution. The organic phase was separated and washed with 40 mL of brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc to 10% MeOH/EtOAc) to give yellow glass. The product was further purified by a prep-HPLC to give yellow glass. MS (ESI pos. ion) m/z: 395 (MH+). Calc'd exact mass for C19H12F2N6S: 394.

المصدر