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

HRID 459760Notes

Reaction equation

HRID 459760 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](=[O:42])[CH2:31][CH:32]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:33]([OH:35])=O>CC(N(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:42])[CH2:31][CH:32]([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:33]1=[O:35]

Participants

4

Reactant 2

HCID 81531DiisopropylethylamineHCID 18444383N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-2-phenylsuccinamic acid

Product 1

HCID 115609611-[2-Fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-3-phenylpyrrolidine-2,5-dioneYield 76.4%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

O-Benzotriazol-1-yl-N,N,N′N′-tetramethyluronium tetrafluoroborate (0.726 g, 2.26 mmol) and diisopropylethylamine (0.494 g, 3.8 mmol) were added sequentially at ambient temperature to a stirred solution of N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-2-phenylsuccinamic acid (0.775 g, 1.7 mmol) in dimethylacetamide (4 ml), the mixture was stirred at ambient temperature for 65 hours, then it was added dropwise to ice-cold water (40 ml). The resulting solid was collected by filtration, washed with water (3 ml), then dried in vacuo. The crude product was dissolved in hot methanol (8 ml), the solution was filtered through a small plug of cotton wool, then the filtrate was added to water (30 ml). 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-phenylpyrrolidine-2,5-dione (0.555 g) as an off-white solid, m.pt. 114–120° C.; 250 MHz 1H-nmr (CDCl3) δ (ppm): 2.8–3.0 (m, 1H) (—CHHCHPh), 3.2–3.4 (m, 1H) (—CHHCHPh), 4.1–4.3 (m, 1H+2H) (—CHPh- and ArCH2—), 7.0–7.4 (m, 8H) (8×ArH), 7.6–7.8 (m, 3H) (3×ArH), 8.4 (d, 1H) (ArH), 10.65 (s, 1H) (CONH); m/z (M+H)+. 428, 92.1% purity.

Workup

  1. filtrationThe resulting solid was collected by filtration
  2. washwashed with water (3 ml)
  3. customdried in vacuo
  4. dissolutionThe crude product was dissolved in hot methanol (8 ml)
  5. filtrationthe solution was filtered through a small plug of cotton wool
  6. additionthe filtrate was added to water (30 ml)
  7. filtrationThe resulting solid was collected by filtration
  8. customdried in vacuo

Sources & evidence

ORD record
ord-a8af06d834d1496b9cda6539da32a0eb
Source dataset
uspto-grants-2007_03
Patent number
US07196085B2

Reaction notes

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