Diisopropylethylamine → 4-Benzyl-1-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]piperazine-2,6-dione

HRID 459765Notes

Reaction equation

HRID 459765 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[F:20])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:16])[NH:8][N:7]=1.[CH2:21]([N:28]1[CH2:33][C:32](=O)[O:31][C:30](=[O:35])[CH2:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(C(C)C)CC)(C)C>C1(C)C=CC=CC=1>[CH2:21]([N:28]1[CH2:33][C:32](=[O:31])[N:1]([C:2]2[CH:3]=[C:4]([CH2:5][C:6]3[C:15]4[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=4)[C:9](=[O:16])[NH:8][N:7]=3)[CH:17]=[CH:18][C:19]=2[F:20])[C:30](=[O:35])[CH2:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 184443734-(3-amino-4-fluorobenzyl)-2H-phthalazin-1-oneHCID 218153894-Benzylmorpholine-2,6-dione

Product 1

HCID 184443764-Benzyl-1-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]piperazine-2,6-dione

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A stirred mixture of 4-(3-amino-4-fluorobenzyl)-2H-phthalazin-1-one (2.51 g, 9.3 mmol; prepared in a manner similar to that described in Example 23), 4-benzylmorpholin-2,6-dione (2.3 g, 11.2 mmol) and toluene (15 ml) was heated under reflux for 20 hours, then the solvent was removed in vacuo. The residue was dissolved in dimethylacetamide (15 ml) and O-benzotriazol-1-yl-N,N,N′N′-tetramethyluronium tetrafluoroborate (3 g, 9.3 mmol) and diisopropylethylamine (1.63 ml, 9.3 mmol) were added sequentially. The mixture was stirred at ambient temperature for 2 hours, then it was added dropwise to stirred, ice-cold water (300 ml). The resulting solid was collected by filtration and dried in vacuo to give 4-benzyl-1-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]piperazine-2,6-dione (4.01 g) as an off-white solid, 250 MHz 1H-nmr (d6-DMSO) δ (ppm): 3.6 (s, 4H) (2×ring CH2) 3.75 (s, 2H) (NCH2Ph), 4.35 (s, 2H) (ArCH2—), 7.17–7.5 (m, 8H) (8×ArH), 7.75–8.0 (m, 3H) (3×ArH), 8.25 (d, 1H) (ArH), 12.6 (s, 1H) (CONH); m/z (M+H)+ 457, 100% purity.

Workup

  1. customprepared in a manner similar to
  2. temperaturewas heated
  3. temperatureunder reflux for 20 hours
  4. customthe solvent was removed in vacuo
  5. dissolutionThe residue was dissolved in dimethylacetamide (15 ml)
  6. additionit was added dropwise
  7. stirringto stirred
  8. filtrationThe resulting solid was collected by filtration
  9. customdried in vacuo

Sources & evidence

ORD record
ord-e83fbe8598a34e728abbf64d7e75343e
Source dataset
uspto-grants-2007_03
Patent number
US07196085B2

Reaction notes

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