Ethanol → HCID 10166015, Verbindung

To a flask containing 1-[1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-3-(3,5-dichloro-phenyl)-1-methyl-urea (0.094 g, 0.164 mmol) was added Pd(PPh3)4 (0.02 g, 0.017 mmol, 10 mol %), 3-cyanophenylboronic acid (0.037 g, 0.25 mmol, 1.5 eq.) and Na2CO3 (0.212 g, 2 mmol). The mixture was suspended in toluene (3 mL), EtOH (1.5 mL) and H2O (1 mL) and heated to 80° C. for 18 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (5 mL) and saturated Na2CO3 (5 mL). The organic layer was washed with saturated Na2CO3 (3×5 mL), saturated brine (3×5 mL), dried over anhydrous sodium sulfate, filtered and concentrated by rotary evaporation to give a brown solid which was purified by HPLC to give the title compound 1-[4-(3′-cyano-biphenyl-4-yl)-1-cyclopropylmethyl-piperidin-4-yl methyl]-3-(3,5-dichloro-phenyl)-1-methyl-urea (0.053 g, 60%). 1H NMR (300 MHz, CDCl3): δ 7.95 (s, 1H), 7.92 (d, 1H), 7.79-7.66 (m, 4H), 7.57 (d, 2H), 7.41 (s, 2H), 7.33 (br.s, 1H), 7.06 (s, 1H), 3.76 (m, 2H), 3.63 (s, 1H), 3.60 (s, 2H), 3.08 (s, 3H), 2.87 (br.m, 2H), 2.69 (m, 5H), 1.14 (br.m, 1H), 0.84 (d, 2H), 0.44 (d, 2H)

1. custompartitioned between EtOAc (5 mL) and saturated Na2CO3 (5 mL)
2. washThe organic layer was washed with saturated Na2CO3 (3×5 mL), saturated brine (3×5 mL)
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated by rotary evaporation
6. customto give a brown solid which
7. customwas purified by HPLC

ORD-Eintrag

ord-f93f0b5a5dd14e3c9b37e6b3fbde13f3

Quelldatensatz

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06887889B2