Diisopropylamine → 4'-[2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethoxy]-3-(isopropylthio)-N-(methylsulfonyl)-4-biphenylcarboxamide hydrochloride

Temperature

100 °C

To a solution of 4-[(1R,2S)-2-amino-1-hydroxypropyl]-phenol (96.6 mg) in N,N-dimethylformamide (1.00 ml) were added diisopropylamine (156 μl) and 4′-(2-bromoethoxy)-3-(isopropylthio)-N-(methylsulfonyl)-4-biphenylcarboxamide (210 mg) at room temperature and stirred at 100° C. for 5 hours. To the reaction mixture was added hydrogen chloride 1,4-dioxane solution (4M, 464 μl) and stirred at 0° C. The mixture was filtrated and the filtrate was concentrated in vacuo. The residue was washed with ethyl ether three times, dried and purified with reverse phase silica gel column chromatography. To the resulting solution was added hydrogen chloride ethyl acetate solution (4M, 111 μl) and concentrated in vacuo to give 4′-[2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethoxy]-3-(isopropylthio)-N-(methylsulfonyl)-4-biphenylcarboxamide hydrochloride (108 mg).

1. stirringstirred at 0° C
2. filtrationThe mixture was filtrated
3. concentrationthe filtrate was concentrated in vacuo
4. washThe residue was washed with ethyl ether three times
5. customdried
6. custompurified with reverse phase silica gel column chromatography
7. additionTo the resulting solution was added hydrogen chloride ethyl acetate solution (4M, 111 μl)
8. concentrationconcentrated in vacuo

ORD record

ord-eb0ba98dc4da42bdbb1d0539054491c1

Source dataset

uspto-grants-2008_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07417060B2