Diisopropylethylamine → 4-(((3R,4R)-3-ethyl-1-((S)-2-hydroxybutanoyl)piperidin-4-yl)amino)-6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide

To a solution of (S)-2-hydroxybutanoic acid (3.54 mg, 0.034 mmol) in DMF (181 μl) were added DIEA (28.5 μl, 0.163 mmol) and HATU (25.9 mg, 0.068 mmol). After 15 minutes, 4-(((3R,4R)-3-ethylpiperidin-4-yl)amino)-6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide (10 mg, 0.027 mmol) was added. The reaction was stirred at room temperature for 3 hrs. The product mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried with sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified via preparative HPLC (Column: Waters XBridge C18, 19×200 mm, 5-μm). The collected fractions were combined and dried via centrifugal evaporation to yield the title compound (7.9 mg, 0.017 mmol, 64.0% yield) as a white solid. 1H NMR (500 MHz, 1:1 Chloroform-d/Methanol-d4) δ 8.12-8.09 (m, 1H), 7.77 (d, J=2.5 Hz, 1H), 7.72 (d, J=3.5 Hz, 2H), 6.92-6.88 (m, 1H), 4.42-4.34 (m, 2H), 4.24-4.13 (m, 1H), 3.95 (s, 3H), 3.12-3.03 (m, 1H), 2.41-2.34 (m, 1H), 1.84-1.73 (m, 2H), 1.70-1.58 (m, 3H), 1.43-1.32 (m, 1H), 1.06-0.97 (m, 7H). LCMS (Method K) m/z 454.249 ([M+H]+). HPLC (Method F) Rt: 1.12 min.

1. customThe product mixture was partitioned between ethyl acetate and water
2. washThe organic layer was washed with brine
3. dry with materialdried with sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe crude product was purified via preparative HPLC (Column: Waters XBridge C18, 19×200 mm, 5-μm)
7. customdried via centrifugal evaporation

ORD 기록

ord-16b8356882bf4ae7adc01aa3633f3607

출처 데이터셋

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08987268B2