Reacción #1244301

Ecuación de reacción

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

Rendimiento 65.0%

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

Rendimiento 65.0%

Disolventes

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroquenched with H2O (10 mL)
2. 2
   workup.ADDITIONdiluted with CH2Cl2 (50 mL)
3. 3
   LavadoThe organic layer was washed with 1 N HC, (3×50 mL), saturated NaHCO3 (3×50 mL), and brine (2×25 mL)
4. 4
   Secadodried over MgSO4

Procedimiento

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.

Fuente