反応 #674303

反応方程式

(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

収率 88.2%

溶媒

formic acid

EtOAc

反応条件

後処理

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

実験手順

(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.

出典