Reacción #2275737

Ecuación de reacción

TBAF

N-({1-[4-(5-Iodo-2-oxo-2H-pyridin-1-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

ethynyl-trimethyl-silane

→

title compound

N-({1-[4-(5-Ethynyl-2-oxo-2H-pyridin-1-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   FiltraciónThe solid was filtered off
2. 2
   Otrothe residue was partitioned between water
3. 3
   SecadoThe organic layer was dried over anhydrous Na2SO4
4. 4
   Filtraciónfiltered
5. 5
   Concentraciónconcentrated
6. 6
   Otroto give the crude product, which
7. 7
   OtroThe solvent was removed
8. 8
   Otrothe residue was then purified by a CombiFlash® system

Procedimiento

N-({1-[4-(5-Iodo-2-oxo-2H-pyridin-1-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide (as prepared in Example 8, Step C, 450 mg, 0.75 mmol), ethynyl-trimethyl-silane (Fluka, 100 mg, 1.02 mmol), Pd(Ph3P)2Cl2 (Aldrich, 0.02 mmol), CuI (Aldrich, 0.02 mmol) and TEA (1 mL) were mixed in THF (6 mL) at room temperature under argon. The reaction was stirred overnight. The solid was filtered off and the residue was partitioned between water and a chloroform/IPA “cocktail” (˜3:1, v/v). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated to give the crude product, which was treated with TBAF (Aldrich, 1.0 N in THF, 2 mL) for 30 min. at room temperature. The solvent was removed and the residue was then purified by a CombiFlash® system using ethyl acetate and 7N NH3 in MeOH as eluent (from pure ethyl acetate to 5% 7N NH3 in MeOH in ethyl acetate) to afford the title compound as yellow solid.

Fuente