1-Hydroxybenzotriazole → methyl N-{5-[(N-acetyl-4-amino-3-isopropylphenylalanyl)amino]pentanoyl}methioninate

HRID 488653Notes

Reaction equation

HRID 488653 reaction equation
[C:1]([NH:4][C@H:5]([C:17]([O:19]C)=O)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[C:9]([CH:14]([CH3:16])[CH3:15])[CH:8]=1)(=[O:3])[CH3:2].[CH3:21][O:22][C:23](=[O:37])[CH:24]([NH:29][C:30](=[O:36])[CH2:31][CH2:32][CH2:33][CH2:34][NH2:35])[CH2:25][CH2:26][S:27][CH3:28].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>[OH-].[Na+].CO.CN(C=O)C.O.C(N(CC)CC)C>[C:1]([NH:4][C@H:5]([C:17]([NH:35][CH2:34][CH2:33][CH2:32][CH2:31][C:30]([NH:29][C@H:24]([C:23]([O:22][CH3:21])=[O:37])[CH2:25][CH2:26][S:27][CH3:28])=[O:36])=[O:19])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[C:9]([CH:14]([CH3:15])[CH3:16])[CH:8]=1)(=[O:3])[CH3:2]

Participants

10

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69803103methyl N-acetyl-4-amino-3-isopropylphenylalaninateHCID 865853262-(5-Amino-pentanoylamino)-4-methylsulfanyl-butyric acid methyl ester

Product 1

HCID 69799946methyl N-{5-[(N-acetyl-4-amino-3-isopropylphenylalanyl)amino]pentanoyl}methioninate

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of methyl N-acetyl-4-amino-3-isopropylphenylalaninate in 1N NaOH (4 mL) and methanol (2 mL) was stirred for 5 hours, concentrated under reduced pressure, taken up in a mixture of ethyl acetate and ethanol (3×30 mL, 1:1), dried (Na2SO4), filtered and concentrated under reduced pressure. MS (ESI) m/z=−263 (M−H)−. To a mixture of the residue (239 mg, 0.833 mmole), 2-(5-amino-pentanoylamino)-4-methylsulfanyl-butyric acid methyl ester (298 mg, 1.0 mmole), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (240 mg, 1.25 mmole) and N-hydroxybenzotriazole (169 mg, 1.25 mmole) in DMF (3 mL) was added triethyl amine (116 μL) and the mixture was stirred for 16 hours. The mixture was diluted with water and extracted with ethyl acetate (2×25 mL) then with chloroform (2×25 mL). The combined organics were dried (MgSO4), filtered, concentrated under reduced pressure and purified on silica gel eluting with 30% methanol/ethyl acetate to provide the titled compound (316 mg). MS (ESI) m/z=+509(M+H)+, 531 (M+Na)+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additiontaken up in a mixture of ethyl acetate and ethanol (3×30 mL, 1:1)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. stirringthe mixture was stirred for 16 hours
  7. extractionextracted with ethyl acetate (2×25 mL)
  8. dry with materialThe combined organics were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. custompurified on silica gel eluting with 30% methanol/ethyl acetate

Sources & evidence

ORD record
ord-dbb6c06d5f2248ddb9183a5e73c040cd
Source dataset
uspto-grants-2005_12
Patent number
US06972340B2

Reaction notes

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