Indomethacin → N-cyclohexyl-N-thiazol-2-yl-1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetamide

Temperatur

100 °C

To a suspension of 2 g (0.02 mol) of N-Cyclohexyl-N-thiazol-2-yl amine in 20 mL of acetonitrile at rt was added 6.1 mL (0.044 mol) of triethylamine and 10.24 g (0.022 mol) of PyBroP [bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (Aldrich or NovaBiochem)]. To the reaction mixture was then added 3.93 g (0.01 mol) of 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid and the reaction mixture was heated at 100° C. for 4 h. The reaction mixture was then cooled to 0° C. and the white precipitate was isolated by filtration. The filtrate was concentrated to ˜10 mL, recooled to 0° C., refiltered and the filtrate was concentrated to an oil. The residue was dissolved in 100 mL of dichloromethane and the solution was washed twice with 1N HCl, and once with 1N NaHCO3 solution. The organic phase was dried (Na2SO4) filtered and the filtrate was concentrated. The residue was purified by chromatography (silica, 0-50% EtOAc in heptane) to give the title compound. 1H NMR (CDCl3) δ 7.74 (1H, d), 7.66 (2H, d), 7.50 (2H, d), 7.40 (1H, d), 6.95 (1H, bs), 6.82 (1H, d), 6.67 (1H, dd), 4.59 (1H, bt), 3.84 (3H, s), 3.61 (2H, s), 2.22 (3H, s), 0.9-2.0 (10H, m)

1. temperatureThe reaction mixture was then cooled to 0° C.
2. customthe white precipitate was isolated by filtration
3. concentrationThe filtrate was concentrated to ˜10 mL
4. customrecooled to 0° C.
5. concentrationthe filtrate was concentrated to an oil
6. dissolutionThe residue was dissolved in 100 mL of dichloromethane
7. washthe solution was washed twice with 1N HCl
8. dry with materialThe organic phase was dried (Na2SO4)
9. filtrationfiltered
10. concentrationthe filtrate was concentrated
11. customThe residue was purified by chromatography (silica, 0-50% EtOAc in heptane)

ORD-Eintrag

ord-2b513d369b9548f2a8472f6b0ff0cf68

Quelldatensatz

uspto-grants-2008_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07414067B2