反应详情

A solution of triphosgene (4 mg, 0.01 mmol) in DCM (0.8 mL) was cooled to 0° C. A solution of 7-[(R)-1-(2,6-dichloro-3-fluorophenyl)-ethoxy]-3-(1,2,3,6-tetrahydropyridin-4-yl)-furo[3,2-c]pyridin-6-ylamine (10.0 mg, 0.0237 mmol), DIPEA (0.04 mL, 0.2 mmol) and DCM was added, and the mixture was allowed to warm to rt. A solution of tert-butyl 1-piperazinecarboxylate (8.82 mg, 0.0474 mmol) in DCM was then added, and the mixture was stirred at rt for 30 min. The material was transferred to a separatory funnel and washed with sat. aq. NaHCO3. The organic layer was concentrated in vacuo, redissolved in dioxane and transferred to a sealed tube. 4 M HCl in 1,4-dioxane (0.2 mL) was added, and the solution was heated to 50° C. for 3 h. The material was concentrated in vacuo and redissolved in DMF (0.5 mL). The solution was purified by HPLC. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a brown solid. 1H NMR (CD3OD, 400 MHz): δ=1.89 (d, J=6.8 Hz, 3H), 2.56 (br, s, 2H), 3.21-3.29 (m, 4H), 3.44-3.52 (m, 4H), 3.56 (t, J=5.8 Hz, 2H), 4.08 (d, J=2.5 Hz, 2H), 6.26 (br, s, 1H), 6.50 (q, J=6.7 Hz, 1H), 7.22 (t, J=8.7 Hz, 1H), 7.40 (dd, J=9.0, 4.9 Hz, 1H), 7.66 (s, 1H), 8.19 (s, 1H). MS (ES+): m/z 534.14 [MH+]. HPLC: tR=2.16 min (ZQ2, polar—5 min).

1. customThe material was transferred to a separatory funnel
2. washwashed with sat. aq. NaHCO3
3. concentrationThe organic layer was concentrated in vacuo
4. dissolutionredissolved in dioxane
5. customtransferred to a sealed tube
6. addition4 M HCl in 1,4-dioxane (0.2 mL) was added
7. temperaturethe solution was heated to 50° C. for 3 h
8. concentrationThe material was concentrated in vacuo
9. dissolutionredissolved in DMF (0.5 mL)
10. customThe solution was purified by HPLC
11. additionThe fractions containing the pure product
12. concentrationwere concentrated in vacuo