Potassium Hydroxide → N-cyclopropyl-2-(4-fluorophenyl)-3-(4-((E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl)phenyl)acrylamide

Hydroxylamine hydrochloride (0.86 g, 12.3 mmol) in methanol (3 mL) was mixed with KOH (0.69 g, 12.3 mmol) in methanol (3 mL) at 0° C., and sonicated for 2 minutes, the white precipitate formed was filtered. The filtrate was added to methyl 3-(E)(4-(3-(cyclopropylamino)-2-(4-fluorophenyl)-3-oxoprop-1-en-1-yl)phenyl)acrylate (0.25 g, 0.68 mmol) in DCM (1.5 mL) and the mixture was stirred at room temperature, for 30 minutes. The reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (2×150 mL). The ethyl acetate layer was dried over anhydrous Na2SO4 and concentrated to obtain a sticky compound, which was triturated with DCM (15 mL). The pale brown solid obtained was filtered and washed with DCM (3×5 mL) to afford the title compound (0.07 g, 28% yield). 1H NMR (DMSO-d6) δ (ppm): 0.49-0.53 (2H, dd, —CH2), 0.61-0.66 (2H, m, —CH2), 2.72-2.77 (1H, m, —CH), 6.38-6.42 (1H, d, ═CH), 7.00-7.02 (2H, d, Ar—H), 7.16-7.27 (5H, m, Ar—H and ═CH), 7.33-7.43 (3H, m, Ar—H and ═CH), 7.81-7.82 (1H, d, —NH), 9.04 (1H, s, —OH), 10.73 (1H, s, —NH). MS m/z: 367.1 (M++1).

1. customsonicated for 2 minutes
2. customthe white precipitate formed
3. filtrationwas filtered
4. extractionextracted with ethyl acetate (2×150 mL)
5. dry with materialThe ethyl acetate layer was dried over anhydrous Na2SO4
6. concentrationconcentrated
7. customto obtain a sticky compound, which
8. customwas triturated with DCM (15 mL)
9. customThe pale brown solid obtained
10. filtrationwas filtered
11. washwashed with DCM (3×5 mL)

ORD record

ord-a897707854634858aed52edec8711fe6

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450525B2