Triethylamine → N1-(3-Fluoro-4-hydroxyphenyl)-N3-(4-fluorophenyl)malonamide

HRID 347482Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[CH2:10][C:11]([OH:13])=O)=[CH:4][CH:3]=1.C(N(CC)CC)C.[NH2:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[C:25]([F:30])[CH:24]=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[F:30][C:25]1[CH:24]=[C:23]([NH:22][C:11](=[O:13])[CH2:10][C:9]([NH:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[O:14])[CH:28]=[CH:27][C:26]=1[OH:29]

Participants

Conditions

Temperature: 0 °C

Procedure

3-(4-Fluorophenylamino)-3-oxopropanoic acid (197 mg, 1.00 mmol) was dissolved in 4 mL of dimethylformamide. Triethylamine (140 μL, 1.00 mmol) was added and the solution was cooled to 0° C. 4-Amino-2-fluorophenol (127 mg, 1.00 mmol, Aldrich) was added followed BOP reagent (442 mg, 1.00 mmol). The reaction was allowed to warm to room temperature and was then stirred at room temperature for 3 h. The reaction mixture was concentrated to remove methylene chloride and water was added to precipitate the product. Filtration and trituration with water gave the title compound (211 mg, 69%) as a white solid. 1H NMR (CD3OD) δ 7.61 (m, 2H), 7.51 (dd, 1H, J=13, 2.5 Hz), 7.08 (m, 3H), 6.88 (t, 1H, J=9.4 Hz), 3.51 (s, 2H); MS(ESI+) m/z 307.4 (M+H)+.

Workup

temperatureto warm to room temperature
concentrationThe reaction mixture was concentrated
customto remove methylene chloride and water
additionwas added
customto precipitate the product
filtrationFiltration and trituration with water

Sources & evidence

ORD record: ord-d8d3199cecf04ecbaff54427cecbbc1a
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07173031B2

Reaction notes

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