(2S)-2-amino-N,4-dimethylpentanamide → [(2,5-dioxo-1-imidazolidinyl)methyl][(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinic acid ethyl ester

HRID 476722Notes

Reaction equation

HRID 476722 reaction equation
[CH2:1]([O:3][P:4]([CH2:14][CH:15]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:16]([OH:18])=O)([CH2:6][N:7]1[C:11](=[O:12])[CH2:10][NH:9][C:8]1=[O:13])=[O:5])[CH3:2].[CH3:23][NH:24][C:25](=[O:32])[C@H:26]([CH2:28][CH:29]([CH3:31])[CH3:30])[NH2:27]>ClCCl.O1CCCC1>[CH2:1]([O:3][P:4]([CH2:6][N:7]1[C:11](=[O:12])[CH2:10][NH:9][C:8]1=[O:13])([CH2:14][CH:15]([C:16](=[O:18])[NH:27][C@H:26]([C:25](=[O:32])[NH:24][CH3:23])[CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:19][CH:20]([CH3:22])[CH3:21])=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 11672684(2S)-2-amino-N,4-dimethylpentanamideHCID 200630052(RS)-[[(RS)-(ethoxy)[(2,5-dioxo-1-imidazolidinyl)-methyl]phosphinyl]methyl]-4-methylvaleric acid

Product 1

HCID 67864219[(2,5-dioxo-1-imidazolidinyl)methyl][(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinic acid ethyl esterYield 27.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

0.22 g (0.64 mmol) of 2(RS)-[[(RS)-(ethoxy)[(2,5-dioxo-1-imidazolidinyl)methyl]phosphinyl]methyl]-4-methylvaleric acid and 0.116 g (0.81 mmol) of L-leucine methylamide were taken up in 5 ml of dichloromethane and 2.5 ml of tetrahydrofuran. The solution was treated at -8° C. with 0.3 g (1.2 mmol) of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline. The mixture was stirred at room temperature for 24 hours and was then left to stand at 0° C. for 48 hours. The solvent was removed by evaporation. The residue was taken up in 50 ml of chloroform. The solution was washed in sequence with 5% citric acid solution, 5% sodium hydrogen carbonate solution and sodium chloride solution, dried over anhydrous sodium sulfate and evaporated to give a gum. This gum was chromatographed on silica gel using chloroform/methanol (19:1) for the elution to give 0.08 g of [(2,5-dioxo-1-imidazolidinyl)methyl][(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinic acid ethyl ester as a gum.

Workup

  1. waitwas then left
  2. waitto stand at 0° C. for 48 hours
  3. customThe solvent was removed by evaporation
  4. washThe solution was washed in sequence with 5% citric acid solution, 5% sodium hydrogen carbonate solution and sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated
  7. customto give a gum
  8. customThis gum was chromatographed on silica gel
  9. washfor the elution

Sources & evidence

ORD record
ord-7a0e0e5f8b5e4c03a9c3206178bd574a
Source dataset
uspto-grants-1989_12
Patent number
US04885283

Reaction notes

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