2-(Methylamino)ethanol → HCID 54670800, Verbindung

To a solution of (S)-4-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid (Example 153, Step B; 0.1 g, 0.22 mmol) in DMF (2 mL) was added HATU (0.17 g, 0.44 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.12 mL, 0.66 mmol) and the reaction was stirred for 20 minutes at ambient temperature. 2-(Methylamino)ethanol (0.050 g, 0.66 mmol) was added, and the reaction was stirred for 2 hours at ambient temperature. The reaction was diluted with EtOAc (30 mL) and washed with HCl (1 N, 10 mL), NaOH (1 N, 10 mL), water (10 mL), and brine (10 mL), and the combined organic phases were dried over MgSO4, filtered and concentrated under vacuum. The crude material was purified by reverse phase HPLC. The combined fractions were diluted with EtOAc (50 mL) and washed with 1 N NaOH (10 mL), water (10 mL), and brine (10 mL), and the combined organic phases were dried over MgSO4, filtered and concentrated under vacuum to give (S)-4-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluoro-N-(2-hydroxyethyl)-N-methylbenzamide (0.033 g, 0.064 mmol, 29% yield). Mass spectrum (apci) m/z=509.0 (M+H).

1. stirringthe reaction was stirred for 2 hours at ambient temperature
2. washwashed with HCl (1 N, 10 mL), NaOH (1 N, 10 mL), water (10 mL), and brine (10 mL)
3. dry with materialthe combined organic phases were dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated under vacuum
6. customThe crude material was purified by reverse phase HPLC
7. additionThe combined fractions were diluted with EtOAc (50 mL)
8. washwashed with 1 N NaOH (10 mL), water (10 mL), and brine (10 mL)
9. dry with materialthe combined organic phases were dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated under vacuum

ORD-Eintrag

ord-ca8f5216ec1d46678a9217db3f7a89dc

Quelldatensatz

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08754226B2