反应详情

温度

80 °C

2-Chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5′-fluoro-[3,3′-bipyridine]-5-carboxamide (Stage 266.1, 80 mg, 0.183 mmol) and DIPEA (0.224 mL, 1.282 mmol) were added to a vial containing iPrOH (2 mL) and 4-(aminomethyl)pyrrolidin-3-ol dihydrochloride (Stage 267.1, 37.1 mg, 0.192 mmol) was added under an argon atmosphere. The RM was stirred at 80° C. for 3 days. The RM was treated with sat. aq. Na2CO3 (20 mL) and extracted with EtOAc. The combined extracts were washed with brine (10 mL), dried over Na2SO4, filtered and evaporated to dryness under reduced pressure to give the crude product was purified by preparative HPLC (Condition 14). Fractions containing product were treated with sat. aq. Na2CO3 and the MeCN was evaporated off under reduced pressure. The resulting aq. residue was extracted with EtOAc and the combined extracts were dried over Na2SO4, filtered and evaporated. The residue was suspended in DCM/Et2O/n-hexane. The obtained solid was filtered off, washed with Et2O, n-hexane and dried to afford the title product as a white solid. HPLC (Condition 10) tR=5.74 min, UPLC-MS (Condition 3) tR=0.83 min, m/z=508 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.41-3.33 (m, 7H) 3.92-4.21 (m, 1H) 7.34 (d, J=8.99 Hz, 2H) 7.85 (d, J=9.38 Hz, 3H) 8.03-8.11 (m, 1H) 8.47-8.54 (m, 1H) 8.59 (m, J=2.70 Hz, 1H) 8.77 (m, J=2.30 Hz, 1H) 10.19 (s, 1H).

1. additionwas added under an argon atmosphere
2. extractionextracted with EtOAc
3. washThe combined extracts were washed with brine (10 mL)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. customevaporated to dryness under reduced pressure
7. customto give the crude product
8. customwas purified by preparative HPLC (Condition 14)
9. additionFractions containing product
10. additionwere treated with sat. aq. Na2CO3
11. customthe MeCN was evaporated off under reduced pressure
12. extractionThe resulting aq. residue was extracted with EtOAc
13. dry with materialthe combined extracts were dried over Na2SO4
14. filtrationfiltered
15. customevaporated
16. filtrationThe obtained solid was filtered off
17. washwashed with Et2O, n-hexane
18. customdried