Dimethylformamide → HCID 178454150, compound

HRID 1590119Notes

Reaction equation

HRID 1590119 reaction equation
C(N(CC)CC)C.Cl.Cl.[NH2:10][CH2:11][CH2:12][C:13]1[N:17]=[CH:16][NH:15][CH:14]=1.C1(=O)N([O:23][C:24](=O)[C@H:25]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])C(=O)CC1.CN(C)C=O>O>[C:30]([O:29][C:27]([NH:26][C@H:25]([C:24]([NH:10][CH2:11][CH2:12][C:13]1[N:17]=[CH:16][NH:15][CH:14]=1)=[O:23])[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:28])([CH3:32])([CH3:33])[CH3:31]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 107447tert-Butyl (S)-(1-benzyl-2-((2,5-dioxo-1-pyrrolidinyl)oxy)-2-oxoethyl)carbamateHCID 178478691HCID 178478691, compound

Product 1

HCID 178454150HCID 178454150, compoundYield 69.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Triethylamine (3.5 ml) is added to a mixture of histamine dihydrochloride (1.84 g), N-tert-butoxycarbonyl-L-phenylalanine succinimido ester (3.62 g), dimethylformamide (20 ml) and water (5 ml) under ice-cooling and then the mixture is stirred at room temperature for three hours. The reaction mixture is concentrated under reduced pressure to remove solvent and ethyl acetate is added to the residue and then, insoluble materials are filtered off. The filtrate is washed with an aqueous sodium bicarbonate solution and water, dried, and then concentrated to remove solvent. The residue is crystallized with ether to give N-(N-tert-butoxycarbonyl-L-phenylalanyl)histamine (2.5 g). The product (1.79 g) thus obtained is dissolved in 15% hydrogenbromide-acetic acid solution and the solution is stirred at room temperature for 30 minutes. The reaction mixture is concentrated under reduced pressure to give N-(L-phenylalanyl) histamine dihydrobromide (2.1 g). The thus-obtained product (2.1 g) is dissolved in dimethylformamide, and N-tert-butoxycarbonyl-L-phenylalanine succinimido ester (1.81 g) and triethylamine (2.1 ml) are added thereto and then the mixture is stirred overnight. Ethyl acetate is added to the reaction mixture, and insoluble materials are filtered off. The filtrate is washed with an aqueous sodium bicarbonate solution and an aqueous sodium chloride solution and dried, and then concentrated to remove solvent. The residue is purified by silica gel column chromatography (solvent; chloroform:methanol=9:1) and crystallized with ether to give N-(N-tert-butoxycarbonyl-L-phenylalanyl L-phenylalanyl)histamine (1.88 g) as white crystals. Yield ; 74.3%

Workup

  1. temperaturecooling
  2. concentrationThe reaction mixture is concentrated under reduced pressure
  3. customto remove solvent and ethyl acetate
  4. additionis added to the residue
  5. filtrationinsoluble materials are filtered off
  6. washThe filtrate is washed with an aqueous sodium bicarbonate solution and water
  7. customdried
  8. concentrationconcentrated
  9. customto remove solvent
  10. customThe residue is crystallized with ether

Sources & evidence

ORD record
ord-926a95bf1ad24c06bb651b7324491a17
Source dataset
uspto-grants-1993_04
Patent number
US05202312

Reaction notes

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