Water → 4-(4-chlorobenzyl)-2-[5-(N-methyl-N-benzylamino)-1-carboxy-t-butyl-3-pentyl]-1(2H)-phthalazinone

HRID 128700Notes

Reaction equation

HRID 128700 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:21]=[CH:20][C:7]([CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[NH:11][N:10]=2)=[CH:6][CH:5]=1.C([O:26][C:27](=[O:47])[CH2:28][CH2:29][CH:30](OS(C)(=O)=O)[CH2:31][CH2:32][N:33]([CH3:41])[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)(C)(C)C.O>CC(N(C)C)=O>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[N:11]([CH:30]([CH2:31][CH2:32][N:33]([CH3:41])[CH2:34][C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH2:29][CH:28]([C:7]([CH3:20])([CH3:8])[CH3:6])[C:27]([OH:26])=[O:47])[N:10]=2)=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 1044524-(4-chlorobenzyl)phthalazin-1(2H)-oneHCID 193747646-(N-methyl-N-benzylamino)-4-methylsulfonyloxy-caproic acid-t-butyl ester

Product 1

HCID 677840344-(4-chlorobenzyl)-2-[5-(N-methyl-N-benzylamino)-1-carboxy-t-butyl-3-pentyl]-1(2H)-phthalazinone

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
50 °C

Procedure

3 g sodium hydride (80%, in white oil) are added to 21.6 g 4(4-chlorobenzyl)-1(2H)-phthalazinone in 200 ml dimethylacetamide (DMA) with cooling in an ice bath. 37 g 6-(N-methyl -N-benzylamino )-4-methylsulfonyloxy-caproic acid-t-butyl ester in 80 ml DMA are then added dropwise with cooling and stirring continued for 0.5 hour. The mixture is allowed to warm slowly--overnight--to room temperature and is then heated for 2 hours to 40° C.-50° C. The mixture is hydrolyzed by addition of 200 ml water with ice cooling. The precipitated oil is separated and dissolved in dichloromethane. After extraction twice with water, the organic phase is dried and concentrated. The residue is chromatographed over silica gel (Eluent: dichloromethane/methanol/ammonia 25% 95:4:1). 3.5 g are obtained (yellow oil).

Workup

  1. temperaturewith cooling in an ice bath
  2. temperaturewith cooling
  3. temperatureto warm slowly
  4. customThe precipitated oil is separated
  5. dissolutiondissolved in dichloromethane
  6. extractionAfter extraction twice with water
  7. customthe organic phase is dried
  8. concentrationconcentrated
  9. customThe residue is chromatographed over silica gel (Eluent: dichloromethane/methanol/ammonia 25% 95:4:1)
  10. custom3.5 g are obtained (yellow oil)

Sources & evidence

ORD record
ord-a3a73084e2704186848bc4e2057b0830
Source dataset
uspto-grants-1995_11
Patent number
US05464838

Reaction notes

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