反应 #1244301

反应方程式

cyclooctyne

4-(1-Fluoro-cyclooct-2-ynylmethyl)benzoic acid

amine

3-(2,5-Dioxo-2,5-dihydro-pyrrol-1-yl)-propylammonium trifluoroacetate

1-hydroxybenzotriazole

→

desired product

收率 65.0%

N-[3-(2,5-Dioxo-2,5-dihydro-pyrrol-1-yl)-propyl]-4-(1-fluorocyclooct-2-ynylmethyl)benzamide

收率 65.0%

溶剂

CH2Cl2

反应条件

后处理

1. 1
   其他quenched with H2O (10 mL)
2. 2
   workup.ADDITIONdiluted with CH2Cl2 (50 mL)
3. 3
   洗涤The organic layer was washed with 1 N HC, (3×50 mL), saturated NaHCO3 (3×50 mL), and brine (2×25 mL)
4. 4
   干燥dried over MgSO4

实验过程

TEA (0.508 mL, 3.65 mmol) was added to a solution of cyclooctyne 3b (0.200 g, 0.768 mmol), amine 13 (0.235 g, 0.875 mmol), O-(7-Azabenzotriazol-1-yl)-N,N,N′,N-tetramethyluronium hexafluorophosphate (HATU, 0.305 g, 0.802 mmol), and 1-hydroxybenzotriazole (HOBT, 0.123 g, 0.802 mmol) in CH2Cl2 (3 mL) at rt. The reaction was stirred for 15 min at rt, quenched with H2O (10 mL), and diluted with CH2Cl2 (50 mL). The organic layer was washed with 1 N HC, (3×50 mL), saturated NaHCO3 (3×50 mL), and brine (2×25 mL) and dried over MgSO4. Chromatography of the crude product (2:1 to 1:1 hexanes/EtOAc) yielded the desired product as a white solid (0.198 g, 65%, Rf=0.30 in 1:1 hexanes/EtOAc), mp 122.0-124.0° C. (dec). IR: 3413, 2931, 2854, 2222, 1705, 1640 cm−1. 1H NMR (CDCl3, 400 MHz): δ 1.39 (m, 1H), 1.74 (m, 2H), 1.81-2.06 (m, 6H), 2.14-2.32 (m, 3H), 3.05 (d, 1H, J=2.8 Hz), 3.09 (s, 1H), 3.40 (q, 2H, J=6.4 Hz), 3.67 (t, 2H, J=6.0 Hz), 6.75 (s, 2H), 6.93 (m, 1H), 7.41 (d, 2H, J=8.0 Hz), 7.81 (d, 2H, J=8.0 Hz). 13C NMR (CDCl3, 100 MHz): δ 20.5, 26.0, 28.1, 29.4, 34.0, 34.8, 36.2, 44.6 (d, J=25.0 Hz), 47.8 (d, J=24.0 Hz), 90.7 (d, J=32.0 Hz), 95.3 (d, J=174.0 Hz), 104.5 (d, J=10.0 Hz), 126.7, 130.5, 132.9, 134.2, 139.6, 167.1, 171.1. 19F NMR (CDCl3, 376 MHz): δ −139.0 (m). FAB—HRMS: Calcd. for C23H26N2O3F+ [M+H]+: 397.1927, found: 397.1920.

来源