反应 #674303

反应方程式

(R)-tert-butyl 2-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate

Na2CO3

H2O

→

(R)-5-(1-(7-azaspiro[3.5]nonan-2-yl)-1H-pyrazol-4-yl)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine

收率 88.2%

溶剂

formic acid

EtOAc

反应条件

后处理

1. 1
   其他The solution was sonicated at room temperature for 90 min (
2. 2
   其他the temperature of sonication bath
3. 3
   浓缩concentrated by rotavapor
4. 4
   其他to give the residue which
5. 5
   其他The layers were separated
6. 6
   萃取The aqueous phase was extracted with DCM (3×30 mL)
7. 7
   洗涤The combined organic phase was washed with brine (30 mL)
8. 8
   干燥dried over anhydrous Na2SO4
9. 9
   浓缩concentrated
10. 10
    其他to give pale yellow solid which
11. 11
    其他was purified by CombiFlash [12 g silica gel column; (MeOH/NH4OH=10/1)/DCM: 0-20%]

实验过程

(R)-tert-butyl 2-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate (105 mg, 0.178 mmol, 1.0 equiv) was dissolved in formic acid (6 mL). The solution was sonicated at room temperature for 90 min (the temperature of sonication bath reached about 40° C. after 90 min). The solution was cooled to room temperature and concentrated by rotavapor to give the residue which was dissolved in EtOAc (20 mL). A solution of Na2CO3 (2.0 M, 20 mL) was added. The mixture was stirred at room temperature for 30 min. H2O (10 mL) was added. The layers were separated. The aqueous phase was extracted with DCM (3×30 mL). The combined organic phase was washed with brine (30 mL), dried over anhydrous Na2SO4, concentrated to give pale yellow solid which was purified by CombiFlash [12 g silica gel column; (MeOH/NH4OH=10/1)/DCM: 0-20%] to afford 77 mg (yield 88%) of (R)-5-(1-(7-azaspiro[3.5]nonan-2-yl)-1H-pyrazol-4-yl)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine as a off-white foam solid.

来源