HCID 58784302, compound → HCID 58784301, compound

HRID 1374688Notes

Reaction equation

HRID 1374688 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[Cl:41])[N:8]([CH2:20][CH2:21][CH2:22][N:23]([CH3:34])[C:24](=[O:33])[CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:9](=[O:19])[NH:10][C:11]=1[CH2:12][O:13][CH2:14][CH2:15][N:16]=[N+]=[N-])=[O:5])[CH3:2]>CCO.[Pd]>[CH2:1]([O:3][C:4]([C:6]1[CH:7]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[Cl:41])[N:8]([CH2:20][CH2:21][CH2:22][N:23]([CH3:34])[C:24](=[O:33])[CH2:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:9](=[O:19])[NH:10][C:11]=1[CH2:12][O:13][CH2:14][CH2:15][NH2:16])=[O:5])[CH3:2]

Participants

4

Reactant 1

HCID 58784302HCID 58784302, compound

Product 1

HCID 58784301HCID 58784301, compoundYield 56.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A solution of 6-(2-azido-ethoxymethyl)-4-(2-chloro-phenyl)-3-{3-[methyl-(3-phenyl-propionyl)-amino]-propyl}-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester (27 mg, 0.046 mmol) in EtOH (5 mL) was hydrogenated in the presence of 5% palladium on calcium carbonate poisoned with lead (10 mg). After 3 h, the catalyst was removed using a filter syringe. The filtrate was concentrated in vacuo to afford 29 mg of thick, colorless oil as crude product (87% pure by analytical HPLC). The crude product was purified by preparative HPLC (from 30% B to 100% B for 10 min, Solvent A=90% H2O-10% MeOH-0.1% TFA Solvent B=10% MeOH-90% H2O-0.1% TFA, at 20 mL/min using column YMC ODS S5 20×100 mm). The desired fractions were combined and concentrated to remove most of the MeOH. The concentrate was taken up in EtOAc (50 mL) and basicified with saturated aqueous NaHCO3 solution. The EtOAc extract was washed with brine, dried (Na2SO4), filtered, concentrated and dried in vacuo to afford 14.5 mg (43%) of purified material as a thick, colorless oil.

Workup

  1. customthe catalyst was removed
  2. concentrationThe filtrate was concentrated in vacuo
  3. customto afford 29 mg of thick, colorless oil as crude product (87% pure by analytical HPLC)
  4. customThe crude product was purified by preparative HPLC (from 30% B to 100% B for 10 min, Solvent A=90% H2O-10% MeOH-0.1% TFA Solvent B=10% MeOH-90% H2O-0.1% TFA, at 20 mL/min using column YMC ODS S5 20×100 mm)
  5. concentrationconcentrated
  6. customto remove most of the MeOH
  7. extractionThe EtOAc extract
  8. washwas washed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customdried in vacuo

Sources & evidence

ORD record
ord-66ee40298028444f8889a33adbae8a69
Source dataset
uspto-grants-2007_01
Patent number
US07166603B2

Reaction notes

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