Hydrochloric Acid → HCID 178490233, compound

HRID 1417195Notes

Reaction equation

HRID 1417195 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][C@@H:5]1[N:10]([C:11](=[O:33])[C@@H:12]([NH:22][C:23](OCC2C=CC=CC=2)=[O:24])[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[CH2:9][CH2:8][N:7]([CH2:34][C:35]([OH:37])=[O:36])[C:6]1=[O:38].[H][H].C(=O)([O-])O.[Na+].O=C1N(O[C:57](=[O:68])[C:58]2[CH:63]=[CH:62][C:61]([NH:64][C:65]([NH2:67])=[NH:66])=[CH:60][CH:59]=2)C(=O)C2C1C1CC2C=C1.[ClH:71]>CO.O1CCOCC1.O.[Pd]>[ClH:71].[NH:64]([C:61]1[CH:62]=[CH:63][C:58]([C:23]([NH:22][C@@H:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=2)[C:11]([N:10]2[CH2:9][CH2:8][N:7]([CH2:34][C:35]([OH:37])=[O:36])[C:6](=[O:38])[C@@H:5]2[CH2:4][CH2:3][CH2:2][NH:1][C:57](=[O:68])[C:58]2[CH:59]=[CH:60][C:61]([NH:64][C:65]([NH2:67])=[NH:66])=[CH:62][CH:63]=2)=[O:33])=[O:24])=[CH:59][CH:60]=1)[C:65]([NH2:67])=[NH:66]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 54085635HCID 54085635, compoundHCID 178418361HCID 178418361, compoundHCID 178512549HCID 178512549, compound

Product 1

HCID 178490233HCID 178490233, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

In 5 ml of methanol was dissolved 250 mg of (S,S)-3-(3-aminopropyl)-4-[2-benzyloxycarbonylamino-3-(4-methoxyphenyl)propionyl]-2-oxopiperazine-1-acetic acid produced in Reference Example 77. To the solution was added 100 mg of 10% Pd-C, and the mixture was stirred for one hour at room temperature in a hydrogen atmosphere. The catalyst was filtered off, and the filtrate was concentrated under reduced pressure to leave an oily substance. The oily substance was dissolved in a mixture of 10 ml of dioxane and 10 ml of water. To the solution was added 210 mg of sodium hydrogencarbonate and 450 mg of 4-guanidinobenzoic acid 3,5-dioxo-4-azatricyclo[5,2,1,0 2,6]deca-8-en-4-ylester. The mixture was stirred for one hour at room temperature. The pH of the reaction mixture was adjusted to 3 with 1N HCl, then dioxane was distilled off under reduced pressure. The remaining aqueous solution was subjected to CHP-20 column chromatography. The fraction eluted with 10% acetonitrile/water was freeze-dried to afford 130 mg of the title compound as an amorphous powdery product.

Workup

  1. customproduced in Reference Example 77
  2. filtrationThe catalyst was filtered off
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customto leave an oily substance
  5. distillationdioxane was distilled off under reduced pressure
  6. washThe fraction eluted with 10% acetonitrile/water
  7. customwas freeze-dried

Sources & evidence

ORD record
ord-819a8f726d96495a98bfddac93120821
Source dataset
uspto-grants-1999_03
Patent number
US05876756

Reaction notes

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