反应详情

A mixture of 5-(1-azetidin-3-yl-1H-pyrazol-4-yl)-3-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine (6.0 mg, 0.014 mmol), formic acid (1.4 μL, 0.037 mmol), TBTU (8.95 mg, 0.0279 mmol), DIPEA (0.02 mL, 0.09 mmol) and DMF (1 mL) was stirred at rt for 30 min. The solution was used directly for HPLC purification. The fractions containing the material were concentrated in vacuo, redissolved in THF and treated with 5M NaOH (0.1 mL) at rt for 10 min. The solution was neutralized with HCl, and loaded into an SCX cartridge. MeOH was used to wash, and the material was ejected with 2M NH3 in MeOH to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.89 (d, J=7.1 Hz, 3 H), 2.92 (s, 6 H), 4.33-4.40 (m, 2 H), 4.42-4.50 (m, 2 H), 5.16-5.25 (m, 1 H), 5.25-5.35 (m, 1 H), 7.15-7.22 (m, 1 H), 7.37 (d, J=1.5 Hz, 1 H), 7.38-7.53 (m, 2 H), 7.68 (s, 1 H), 7.94 (s, 1 H), 8.33 (s, 1H). MS (ES+): m/z 501.06 (100) [MH+]. HPLC: tR=3.35 min (ZQ3, polar—5 min).

1. customThe solution was used directly for HPLC purification
2. additionThe fractions containing the material
3. concentrationwere concentrated in vacuo
4. dissolutionredissolved in THF
5. additiontreated with 5M NaOH (0.1 mL) at rt for 10 min
6. washto wash