反应详情

To a stirring suspension of 6-(((triisopropylsilyl)oxy)methyl)imidazo[1,2-a]pyridine-3-carboxylic acid (61) (70 mg, 0.20 mmol) in anhydrous dichloromethane (5 mL) at room temperature oxalyl chloride was added dropwise (0.05 mL, 2.22 mmol). Then, one drop of anhydrous DMF was added and the reaction mixture was stirred at room temperature for 15 minutes. The solvent was concentrated and the crude solid was added to a stirring solution of methyl 3-(3-(3-amino-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (31) (51.1 mg, 0.18 mmol) in anhydrous pyridine (5 mL) at room temperature. The reaction was stirred for 20 minutes. Water (20 mL) was added to the reaction mixture and extraction with EtOAc afforded a residue after removing organic solvents. To the above residue, was added THF (0.5 mL) and TBAF (1M in THF, 0.30 mL) and the resulting mixture was stirred for 30 minutes. THF was removed and the residue was dissolved in EtOAc (20 mL) and washed with water twice. The organic layers were combined, dried over Na2SO4, filtered and concentrated to give a crude residue which was dissovled in DCM (1 mL) and followed by addition of DIEA (52 mg, 0.40 mmol) and MsCl (46 mg, 0.4 mmol). The reaction was stirred for 10 minutes. The mixture was diluted with DCM (10 mL) and washed with water. The organic layers were combined, dried over Na2SO4, filtered and concentrated to give methyl 3-(3-(4-methyl-3-(6-(((methylsulfonyl)oxy)methyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (133) which was used without further purification. MS m/z 541.1 (M+1)+.

1. additionwas added dropwise (0.05 mL, 2.22 mmol)
2. concentrationThe solvent was concentrated
3. stirringThe reaction was stirred for 20 minutes
4. customafforded a residue
5. customafter removing organic solvents
6. additionTo the above residue, was added THF (0.5 mL) and TBAF (1M in THF, 0.30 mL)
7. stirringthe resulting mixture was stirred for 30 minutes
8. customTHF was removed
9. dissolutionthe residue was dissolved in EtOAc (20 mL)
10. washwashed with water twice
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. customto give a crude residue which
15. stirringThe reaction was stirred for 10 minutes
16. washwashed with water
17. dry with materialdried over Na2SO4
18. filtrationfiltered
19. concentrationconcentrated