Reaction #44713

Reaction equation

N-{4-[(3-amino-1,2-benzisoxazol-4-yl)oxy]-3-fluorophenyl}-N-(2-amino-6-chloro-4-pyrimidinyl)amine

N-{4-[(3-Amino-1,2-benzisoxazol-4-yl)oxy]-3-fluorophenyl}-N-(2-amino-6-chloro-4-pyrimidinyl)amine

(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridine

diisopropylethylamine

→

4-[(4aR,7aR)-Octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-6-({4-[(3-amino-1,2-benz-isoxazol-4-yl)oxy]-3-fluorophenyl}amino)-2-pyrimidinylamine

Solvents

2-ethylhexanol

Conditions

Workup

1. 1
   TemperatureAfter cooling
2. 2
   Filtrationthe reaction mixture is filtered
3. 3
   workup.ADDITIONwater is added
4. 4
   ExtractionThe mixture is extracted repeatedly with ethyl acetate
5. 5
   Dryingthe organic phase is dried over magnesium sulfate
6. 6
   Otherthe solvent is removed under reduced pressure
7. 7
   OtherThe residue is purified by preparative HPLC

Procedure

88 mg (0.23 mmol) of N-{4-[(3-amino-1,2-benzisoxazol-4-yl)oxy]-3-fluorophenyl}-N-(2-amino-6-chloro-4-pyrimidinyl)amine (from example 3) and 114.8 mg (0.91 mmol) of [(4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridine together with 294.1 mg (2.28 mmol) of diisopropylethylamine are dissolved in 4 ml of 2-ethylhexanol, and the mixture is stirred at 150° C. for 3 h. After cooling, the reaction mixture is filtered and water is added. The mixture is extracted repeatedly with ethyl acetate, the organic phase is dried over magnesium sulfate and the solvent is removed under reduced pressure. The residue is purified by preparative HPLC.

Source