反应详情

Lithium perchlorate (52 mg, 0.49 mmol) was added to THF (5 mL) followed by 1,2-epoxy-2-methylpropane (0.43 mL, 4.9 mmol) and the mixture was stirred for 10-15 minutes giving a clear solution. 9-Azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (0.18 g, 0.49 mmol) was added and the reaction mixture was stirred for 72 hours then concentrated in vacuo. The resultant residue was purified by flash chromatography (SiO2, 0-10% MeOH in EtOAc) and the resulting solid extracted several times with ether. The ether extracts were concentrated in vacuo to give 377 (77 mg, 97%). LCMS: RT=7.45 min, [M+H]+=440. 1H NMR δ (ppm) (CDCl3): 8.28 (1H, d, J=2.34 Hz), 7.90 (1H, s), 7.16 (1H, dd, J=8.29, 2.35 Hz), 7.02 (1H, d, J=8.27 Hz), 5.93-5.83 (1H, m), 4.40-4.34 (2H, m), 4.04-3.95 (2H, m), 3.89-3.79 (1H, m), 3.46-3.36 (4H, m), 2.55 (2H, s), 1.63 (6H, d, J=6.64 Hz), 1.15 (6H, s). 1 Exchangeable proton not seen

1. customgiving a clear solution
2. stirringthe reaction mixture was stirred for 72 hours
3. concentrationthen concentrated in vacuo
4. customThe resultant residue was purified by flash chromatography (SiO2, 0-10% MeOH in EtOAc)
5. extractionthe resulting solid extracted several times with ether
6. concentrationThe ether extracts were concentrated in vacuo