Reaction #674303

Reaction equation

(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

Yield 88.2%

Solvents

formic acid

EtOAc

Conditions

Workup

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

Procedure

(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.

Source