Hydrazine → N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

To a 250 mL round-bottomed flask was added 5-chloro-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(3-fluorophenyl)methyl]ethyl}-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide (7.8 g, 14.91 mmol) and hydrazine (14.50 ml, 298 mmol) in tetrahydrofuran (THF) (75 ml) and methanol (75 mL). After 24 h at RT, the precipitate was filtered, the filtrate was concentrated. The crude product was purified on a silica gel column [CHCl3/MeOH/NH4OH, 90:9:1] to give the title compound as a white solid. The free base product was treated with 4M HCl in dioxane (15 mL). After 5 min, the solution was concentrated and dried under vacuum to afford the product (6.8 g, 95%) as an HCl salt: LCMS (ES) m/z 467 (M+H)+, 1H NMR (400 MHz, CD3OD) δ ppm 7.97 (s, 2H), 7.31 (s, 1H), 7.14 (m, 2H), 6.98 (m, 1H), 6.75 (s, 1H), 4.54 (m, 1H), 3.98 (s, 3H), 3.24 (m, 2H), 3.04 (m, 2H).

1. filtrationthe precipitate was filtered
2. concentrationthe filtrate was concentrated
3. customThe crude product was purified on a silica gel column [CHCl3/MeOH/NH4OH, 90:9:1]

ORD record

ord-4112b7584fe44861a410aa5d4179a5f5

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946278B2