Diisopropylethylamine → HCID 86688118, compound

To a solution of (S)-4-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid (0.10 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. (S)-Pyrrolidin-3-ol (0.058 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 preparative HPLC. The combined fractions were diluted with EtOAc (50 mL) and washed with 1N 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)-1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-((S)-3-hydroxypyrrolidine-1-carbonyl)phenoxy)pyrrolidin-2-one (0.0353 g, 0.0678 mmol, 30.6% yield). Mass spectrum (apci) m/z=521.0 (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 preparative HPLC
7. additionThe combined fractions were diluted with EtOAc (50 mL)
8. washwashed with 1N 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 record

ord-45e460a8dcdd45b09543c5fffbb07e7b

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08754226B2