反应详情

温度

60 °C

To a solution of methyl(2S)-2-(tert-butoxy)-2-[(22S)-17,18-difluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate (22 mg, 0.033 mmol, 1 equiv) in MeCN (0.33 mL) was added 2,6-dichloro-1-fluoropyridin-1-ium, tetrafluoroborate salt (8 mg, 0.031 mmol, 1 equiv). The reaction turned dark orange. After 3 h, the reaction was concentrated in vacuo. The crude fluoride product was taken up in 9:1 MeOH:water (1.8 mL) and LiOH.H2O (27 mg, 0.651 mmol, 20 equiv) was added. The reaction was heated to 60° C. for 4 h. Upon cooling to ambient temperature, the reaction was filtered and purified via preparative LC/MS with the following conditions: Column: XBridge C18, 19×200 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 40-90% B over 20 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min to provide the product (1.1 mg, 5%) 1H NMR (400 MHz, CD3OD) δ 8.33 (d, J=1.5 Hz, 1H), 7.97 (d, J=8.1 Hz, 1H), 7.57 (t, J=7.7 Hz, 1H), 7.37-7.33 (m, 1H), 7.32-7.27 (m, 1H), 7.19 (s, 1H), 7.11 (dd, J=12.8, 7.0 Hz, 1H), 6.04 (br. s., 1H), 4.56 (d, J=5.9 Hz, 1H), 3.76-3.48 (m, 4H), 3.28 (d, J=11.0 Hz, 1H), 2.71 (d, J=6.8 Hz, 1H), 2.53 (s, 3H), 2.09-1.64 (m, 10H), 1.28 (s, 9H), 1.27 (s, 3H), 1.19 (d, J=6.1 Hz, 3H); LCMS (ESI, M): 679.3.

1. concentrationthe reaction was concentrated in vacuo
2. temperatureUpon cooling to ambient temperature
3. filtrationthe reaction was filtered
4. custompurified via preparative LC/MS with the following conditions
5. waitGradient: 40-90% B over 20 minutes
6. customa 5-minute hold