Reaction #2161279

Reaction equation

3-Iodo-N-benzhydryl-azetidine

4-[5-(4-fluorobenzyl)-1H-pyrazol-3-yl]pyridine

NaH

→

title compound

4-[1-[1-(diphenylmethyl)azetidin-3-yl]-5-(4-fluorobenzyl)-1H-pyrazol-3-yl]pyridine

Solvents

DMF

Conditions

Workup

1. 1
   OtherThe solvent was removed in-vacuo
2. 2
   workup.ADDITIONthe residue was diluted with H2O
3. 3
   Extractionextracted with EtOAc
4. 4
   WashThe organic layer was washed with H2O, brine
5. 5
   Dryingdried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Otherto yield a crude
8. 8
   workup.ADDITIONmix of regioisomers
9. 9
   OtherThe residue was purified by flash chromatography (5:95 MeOH/CH2Cl2)
10. 10
    Otherto yield
11. 11
    workup.ADDITIONa clean mix of regioisomers that
12. 12
    Otherwere separated by SF chromatography

Procedure

To a solution of 4-[5-(4-fluorobenzyl)-1H-pyrazol-3-yl]pyridine (3.7 g, 14.6 mmol) in DMF (40 mL) was added NaH (0.584 g, 14.6 mmol) and the solution was stirred for 10 minutes under nitrogen. 3-Iodo-N-benzhydryl-azetidine (5.61 g, 16.1 mmol) was then added and the reaction mixture was heated to 110° C. for 2 hours under nitrogen. The solvent was removed in-vacuo and the residue was diluted with H2O and extracted with EtOAc. The organic layer was washed with H2O, brine, dried over MgSO4, filtered and stripped to yield a crude mix of regioisomers. The residue was purified by flash chromatography (5:95 MeOH/CH2Cl2) to yield a clean mix of regioisomers that were separated by SF chromatography to yield the title compound as a lyophilized solid (2.35 g, 34%. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 8.62 (d, 2 H), 7.69 (d, 2 H), 7.42 (d, 4 H), 7.24-7.31 (m, 4 H), 7.14-7.24 (m, 2 H), 7.02-7.09 (m, 2 H), 6.97 (s, 2 H), 6.36-6.39 (m, 1 H), 4.74-4.87 (m, 1 H), 4.57 (s, 1 H), 3.94 (s, 2 H), 3.51-3.62 (m, 4 H); m/z (APCI+) for C32H27N4F 475.3 (M+H)+.

Source