Acetic Anhydride → 1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one

Temperatur

25 °C

A mixture of 2-(2-methyl-3-(piperidin-4-ylamino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Ex. 53, 55 mg, 0.146 mmol) and DIPEA (76 μl, 0.438 mmol, EMD Biosciences, Rockland, Mass.) in DCM (5.8 mL) was set stirring at 25° C. before adding Ac2O (15.16 μl, 0.161 mmol, Sigma Aldrich) dropwise. The reaction was stirred for 30 min before concentrating under reduced pressure. The residue was taken up in DMSO, and purified by reverse-phase preparative HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 5% to 75%). Product-containing fractions were concentrated under reduced pressure and the residue was loaded onto a pre-washed (MeOH, 1 volume) functionalized Si-carbonate column (Silicyle) and allowed to percolate through to provide 2-(34(1-acetylpiperidin-4-yl)amino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (12.2 mg, 20.0%). 1H NMR (MeOH-d4) δ: 7.84-7.88 (m, 1H), 7.60-7.65 (m, 1H), 7.34-7.40 (m, 1H), 7.23 (s, 1H), 4.55-4.63 (m, 1H), 4.34-4.45 (m, 1H), 3.99-4.07 (m, 1H), 3.58-3.66 (m, 2H), 3.39-3.50 (m, 2H), 2.98-3.04 (m, 1H), 2.58 (s, 3H), 2.27-2.36 (m, 2H), 2.18-2.24 (m, 1H), 2.15 (s, 3H), 1.58-1.69 (m, 2H). m/z (ESI, −ve) 417.1 (M−H)−.

1. stirringThe reaction was stirred for 30 min
2. concentrationbefore concentrating under reduced pressure
3. custompurified by reverse-phase preparative HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 5% to 75%)
4. concentrationProduct-containing fractions were concentrated under reduced pressure
5. washa pre-washed (MeOH, 1 volume) functionalized Si-carbonate column (Silicyle)

ORD-Eintrag

ord-2a10bd757faa40348070001e475c50c1

Quelldatensatz

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09394297B2