Reaction #2275737

Reaction equation

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

Solvents

THF

Conditions

Workup

1. 1
   FiltrationThe solid was filtered off
2. 2
   Otherthe residue was partitioned between water
3. 3
   DryingThe organic layer was dried over anhydrous Na2SO4
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated
6. 6
   Otherto give the crude product, which
7. 7
   OtherThe solvent was removed
8. 8
   Otherthe residue was then purified by a CombiFlash® system

Procedure

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.

Source