Diisopropylethylamine → 1-[2-Fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-3-oct-2-enylpyrrolidine-2,5-dione

HRID 459762Notes

Reaction equation

HRID 459762 reaction equation
C(N(C(C)C)CC)(C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21](=[O:28])[NH:20][N:19]=2)=[CH:13][C:12]=1[NH:29][C:30]([CH2:32][CH:33]([CH2:37][CH:38]=[CH:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])[C:34](O)=[O:35])=[O:31]>CN(C)C=O>[F:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21](=[O:28])[NH:20][N:19]=2)=[CH:13][C:12]=1[N:29]1[C:30](=[O:31])[CH2:32][CH:33]([CH2:37][CH:38]=[CH:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])[C:34]1=[O:35]

Participants

4

Reactant 2

HCID 81531DiisopropylethylamineHCID 686228092-{[2-Fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenylcarbamoyl]methyl}-dec-4-enoic acid

Product 1

HCID 686227341-[2-Fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-3-oct-2-enylpyrrolidine-2,5-dioneYield 45.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

O-Benzotriazol-1-yl-N,N,N′N′-tetramethyluronium tetrafluoroborate (0.107 g, 0.33 mmol) and diisopropylethylamine (0.098 ml, 0.56 mmol) were added sequentially at ambient temperature to a stirred solution of 2-{[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenylcarbamoyl]methyl}-dec-4-enoic acid (0.123 g, 0.26 mmol) in dimethylformamide (2 ml), the mixture was stirred at ambient temperature for 48 hours, then it was added dropwise to ice-cold water (10 ml). The product was extracted into ethyl acetate (2×5 ml), the extracts were combined, dried (MgSO4) and the solvent was removed in vacuo. The residue was triturated with hexane (3 ml) and the resulting solid was collected by filtration and dried in vacuo to give 1-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-3-oct-2-enylpyrrolidine-2,5-dione (0.055 g) as an off-white solid, m.pt 138–141° C.; 250 MHz 1H-nmr (d6-DMSO) δ (ppm): 0.7–0.9 (m, 3H) (CH3), 1.1–1.4 (m, 6H) (—CH2CH2CH2CH3) 1.9–2.1 (m, 2H) (—CH2-nBu), 2.3–2.6 (m, 1H+2H) (—CHCH2CH═CH—), 2.8–3.2 (m, 2H) (ring CH2), 4.4 (s, 2H) (ArCH2—), 5.25–5.45 and 5.45–5.7 (2×m, 2×1H) (—CH═CH—) 7.2–7.3 (m, 1H)(ArH), 7.3–7.5 (m, 1H) (ArH), 7.5–7.6 (m, 1H) (ArH), 7.8–8.05 (m, 3H)(3×ArH), 8.3 (d, 1H) (ArH), 12.65 (s, 1H) (CONH); m/z (M+H)+. 462, 90% purity.

Workup

  1. extractionThe product was extracted into ethyl acetate (2×5 ml)
  2. dry with materialdried (MgSO4)
  3. customthe solvent was removed in vacuo
  4. customThe residue was triturated with hexane (3 ml)
  5. filtrationthe resulting solid was collected by filtration
  6. customdried in vacuo

Sources & evidence

ORD record
ord-5f4be4f289854e52989846c1d6c07aa2
Source dataset
uspto-grants-2007_03
Patent number
US07196085B2

Reaction notes

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