反应详情

温度

70 °C

To a solution of methyl(2S)-2-(tert-butoxy)-2-[(22S)-4,17,22,28-tetramethyl-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 (20 mg, 0.031 mmol, 1 equiv) in MeCN (1 mL) was added NCS (4 mg, 0.031 mmol, 1 equiv). After 1 h, the reaction was concentrated in vacuo. The crude chloride was taken up in 9:1 MeOH:water (1.1 mL) and LiOH.H2O (39 mg, 0.918 mmol, 30 equiv) was added. A few drops of THF were added to aid solubility. The reaction was heated to 70° C. for 1.5 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: 60-100% B over 15 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min to provide the product (10 mg, 48%). 1H NMR (500 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.81 (d, J=7.7 Hz, 1H), 7.56 (t, J=7.7 Hz, 1H), 7.41 (d, J=7.7 Hz, 1H), 7.36 (s, 1H), 7.16-7.08 (m, 3H), 6.02-5.67 (m, 1H), 4.60 (d, J=3.3 Hz, 1H), 3.96 (d, J=10.6 Hz, 2H), 3.52 (d, J=8.4 Hz, 1H), 3.42-3.30 (m, 1H), 2.44 (s, 3H), 2.40-2.31 (m, 2H), 2.29 (s, 3H), 2.05-1.51 (m, 10H), 1.20 (br. s., 3H), 1.19 (s, 9H), 1.03 (d, J=5.9 Hz, 3H); LCMS (ESI, M): 673.3.

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: 60-100% B over 15 minutes
6. customa 5-minute hold