Potassium Carbonate → 4-{4-[4-(Morpholine-4-sulfonyl)-phenyl]-pyrimidin-2-ylamino}benzoic Acid

Crude 1-[4-(morpholine-4-sulfonyl)phenyl]ethanone (4.78 g, 18 mmol) was suspended in dimethylormamide dimethylacetal (50 mL) and refluxed for 12 h. The reaction was allowed to cool and the mixture was concentrated to about half of the original volume. The solution was then titurated with hexanes to precipitate the eneamino ketone intermediate. The eneamino ketone was filtered and washed with hexanes (2×50 mL), dried under vacuum, and then taken up in nPrOH (150 mL). To this solution was added added 4-guanidinobenzoic acid, methyl ester, hydrochloride salt (1.1 equiv, 3.7 g) and K2CO3 (3 equiv, 6.4 g). The mixture was stirred at reflux for 24 h. After this time, 10% NaOH (aq, 50 mL) was added, and the mixture was stirred at reflux for another 1 h. The mixture was then cooled to RT and concentrated to about half of the original volume. The pH of the mixture was then adjusted to pH 4–5 to precipitate the acid. 4-{4-[4-(morpholine-4-sulfonyl)phenyl]pyrimidin-2-ylamino}benzoic acid was immediately filtered and washed with water (50 mL), cold EtOH (50 mL), and then dried (4.6 g, 10.5 mmol, 68%): HPLC Retention Time; 6.6 min. (Method B) M+1, 441.0.

1. temperaturerefluxed for 12 h
2. temperatureto cool
3. concentrationthe mixture was concentrated to about half of the original volume
4. customto precipitate the eneamino ketone intermediate
5. filtrationThe eneamino ketone was filtered
6. washwashed with hexanes (2×50 mL)
7. customdried under vacuum
8. additionTo this solution was added
9. temperatureat reflux for 24 h
10. stirringthe mixture was stirred
11. temperatureat reflux for another 1 h
12. concentrationconcentrated to about half of the original volume
13. customto precipitate the acid
14. filtration4-{4-[4-(morpholine-4-sulfonyl)phenyl]pyrimidin-2-ylamino}benzoic acid was immediately filtered
15. washwashed with water (50 mL), cold EtOH (50 mL)
16. customdried (4.6 g, 10.5 mmol, 68%)

ORD-Eintrag

ord-3e451fb9cb51493798408a249da2ae44

Quelldatensatz

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07129242B2