Cesium carbonate → 4-Chloro-3'-(2-cyclopentyl-1-oxoisoindolin-5-yl)biphenyl-3-carboxylic acid

Temperatur

75 °C

5-Bromo-2-cyclopentylisoindolin-1-one (76 mg, 0.27 mmol), 3′-borono-4-chlorobiphenyl-3-carboxylic acid (90 mg, 0.33 mmol), Cs2CO3 (268 mg, 0.82 mmol) and PdCl2(PPh3)2 (22 mg, 0.03 mmol), were dissolved in a mixture of DME-H2O-EtOH (9.1 mL:3 mL:2.2 mL) and heated at 75° C. for 2 hours. The mixture was filtered through celite washed with water and filtrate was acidified with 2.5 M HCl to form the crude acid as a yellow solid. The crude residue was purified using automated prep-HPLC to yield the desired compound (14.3 mg, 12%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.24 (d, J=2.3 Hz, 1H), 7.94 (d, J=8.0 Hz, 1H), 7.78-7.54 (m, 8H), 4.84-4.75 (m, 1H), 4.43 (s, 2H), 2.08-2.00 (m, 2H), 1.83-1.62 (m, 6H). LRMS calcd. for C26H22ClNO3 [M+H]+ 432 found: 432.

1. filtrationThe mixture was filtered through celite
2. washwashed with water and filtrate
3. customto form the crude acid as a yellow solid
4. customThe crude residue was purified

ORD-Eintrag

ord-4fb36a2c42af493d98b67993f3f91242

Quelldatensatz

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08748632B2