Nitrogen → Arq-621

To a solution of (R)-3-chloro-N-[1-(7-chloro-4-oxo-3-phenylamino-3,4-dihydro-quinazolin-2-yl)-but-3-ynyl]-N-[3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propyl]-2-fluoro-benzamide (1.13 g, 1.65 mmol) in methanol (10 ml) and the solution was purged with N2. To this solution was added hydrazine (110 μl). The mixture was then stirred at room temperature and the reaction progress was monitored by HPLC/MS. The reaction mixture was then filtered and solvent was removed from the filtrate. The residue was purified by flash column to afford N-(3-amino-propyl)-3-chloro-N-[(R)-1-(7-chloro-4-oxo-3-phenylamino-3,4-dihydro-quinazolin-2-yl)-but-3-ynyl]-2-fluoro-benzamide (708 mg, 91%) as off-white solid, M.p. 101-103° C. LCMS: m/e 552 [M+H]. 1H NMR (CDCl3): δ 8.13 (d, J=8.8 Hz, 1H), 7.83 (s, 1H), 7.45 (dd, J=4.8 and 2.0 Hz, 1H), 7.32 (m, 1H), 7.22 (t, J=8.0 Hz, 1H), 7.15 (t, J=8.0 Hz, 1H), 7.05 (t, J=8.0 Hz, 1H), 6.95 (m, 1H), 6.84 (t, J=7.2 Hz, 1H), 6.72 (d, J=7.2 Hz, 1H), 6.48 (d, J=7.2 Hz 1H), 3.62 (m, 1H), 3.48 (m, 1H), 3.28 (br, 1H), 3.14 (m, 1H), 3.02 (br, 1H), 2.59 (m, 2H), 2.30 (br, 1H), 2.02 (t, 2.4 Hz, 1H), 1.36 (m, 2H).

1. filtrationThe reaction mixture was then filtered
2. customsolvent was removed from the filtrate
3. customThe residue was purified by flash column

ORD-Eintrag

ord-51d7d0a390044e909766ada919e7e8d7

Quelldatensatz

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08232285B2