Methanesulfonic Acid → (2S)-2-Benzyloxycarbonylamino-3-(3-(t-butoxycarbonylamino)propanoylamino)propanoic acid methyl ester

HRID 726425Notes

Reaction equation

HRID 726425 reaction equation
[CH3:1][O:2][C:3](=[O:25])[C@@H:4]([NH:14][C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])[CH2:5][NH:6][C:7]([O:9]C(C)(C)C)=O.CS(O)(=O)=O.[C:31]([NH:38][CH2:39][CH2:40]C(O)=O)([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(#N)C.O.C(N(CC)CC)C.CN(C=O)C>[CH3:1][O:2][C:3](=[O:25])[C@@H:4]([NH:14][C:15]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:16])[CH2:5][NH:6][C:7](=[O:9])[CH2:40][CH2:39][NH:38][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32]

Participants

10

Reactant 5

HCID 6395Methanesulfonic AcidHCID 757711-HydroxybenzotriazoleHCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10831821(S)-Methyl 2-N-Cbz-3-N-Boc-propanoate

Product 1

HCID 57083146(2S)-2-Benzyloxycarbonylamino-3-(3-(t-butoxycarbonylamino)propanoylamino)propanoic acid methyl ester

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent2×HCID 8471TriethylamineSolvent

Procedure

The product (6.0 g) obtained in the above (3) is dissolved in acetonitrile (10 ml), and thereto is added dropwise a solution of methanesulfonic acid (8.181 g) in acetonitrile (15 ml) at a temperature below 20° C., and the mixture is stirred at room temperature for 30 minutes. At a temperature below 20° C., to the mixture are added dropwise DMF (20 ml), triethylamine (8.608 g) successively, and the mixture is stirred for 10 minutes. To the mixture are added N-Boc-β-alanine (3.547 g) and HOBT.H2O (3.13 g), and then further added thereto WSC.HCl (3.928 g) at a temperature of from 5° to 10° C., and the mixture is stirred for 30 minutes. The mixture is further stirred at room temperature for 12 hours, and poured into water, and extracted three time with ethyl acetate. The organic layer is washed successively with 1N HCl (twice), a saturated aqueous sodium hydrogen carbonate solution (twice) and a saturated brine (twice), and dried over anhydrous magnesium sulfate. The desiccant is removed by filtration, and the filtrate is concentrated under reduced pressure. The residue is purified by silica gel column chromatography (silica gel; 400 g, solvent; chloroform/acetone=3:1 to 2:1). The fractions containing the title compound are concentrated under reduced pressure to give the title compound (6.974 g).

Workup

  1. stirringthe mixture is stirred for 10 minutes
  2. stirringThe mixture is further stirred at room temperature for 12 hours
  3. extractionextracted three time with ethyl acetate
  4. washThe organic layer is washed successively with 1N HCl (twice), a saturated aqueous sodium hydrogen carbonate solution (twice) and a saturated brine (twice), and
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe desiccant is removed by filtration
  7. concentrationthe filtrate is concentrated under reduced pressure
  8. customThe residue is purified by silica gel column chromatography (silica gel; 400 g, solvent; chloroform/acetone=3:1 to 2:1)
  9. additionThe fractions containing the title compound
  10. concentrationare concentrated under reduced pressure

Sources & evidence

ORD record
ord-7b93134c63144c3684db7c3c0ff4227b
Source dataset
uspto-grants-1998_01
Patent number
US05707994

Reaction notes

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