Water → HCID 86618695, Verbindung

To a solution of 2-(4-methoxyphenyl)thieno[2,3-d]pyridazin-7(6H)-one (455 mg, 1.76 mmol) in DMF (5 ml), was added NaH 60% (110 mg, 2.52 mmol) in small portions. The mixture was stirred at rt. for 10 min before addition of tert-butyl (2S)-2-{[(6-{[(methylsulfonyl)oxy]methyl}pyridin-2-yl)oxy]methyl}piperidine-1-carboxylate (672 mg, 1.68 mmol) dissolved in DMF (3 ml). The reaction was stirred at rt. for 16 h, water (150 ml) and DCM (150 ml) added and the phases separated. The aqueous phase was extracted with DCM (150 ml). The combined organic phases were dried through a phase separator and evaporated in vacuo. Purification by silica gel flash chromatography using a 40+M Biotage column with a gradient of 30-100% EtOAc in heptane yielded the title compound as a light yellow solid. Yield: 354 mg (36%). 1H NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 7.61 (m, 2H), 7.46 (t, 1H, J=7.8 Hz), 7.34 (s, 1H), 6.96 (m, 2H), 6.71 (d, 1H, J=7.3 Hz), 6.55 (d, 1H, J=8.2 Hz), 5.47 (s, 2H), 4.50 (m, 1H), 4.30 (m, 2H), 3.94 (d, 1H, J=10.7 Hz), 3.85 (s, 3H), 2.74 (t, 1H, J=12.2 Hz), 1.67-1.20 (m, 15H). MS (ESI+) 563.30 (M+1H+)

1. stirringThe reaction was stirred at rt
2. customthe phases separated
3. extractionThe aqueous phase was extracted with DCM (150 ml)
4. customThe combined organic phases were dried through a phase separator
5. customevaporated in vacuo
6. customPurification by silica gel flash chromatography

ORD-Eintrag

ord-8ab31b070f434f628b2406b9e1d94c37

Quelldatensatz

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07723331B2