Aniline → N-(2-Acetylthiomethyl-4-phenylbutanoyl)-(L)-leucine, N-phenylamide

HRID 1780026Notes

Reaction equation

HRID 1780026 reaction equation
[C:1]([S:4][CH2:5][CH:6]([CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:7]([NH:9][C@H:10]([C:15]([OH:17])=O)[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:8])(=[O:3])[CH3:2].[NH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C>C1COCC1.C(Cl)Cl>[C:27]1([NH:26][C:15](=[O:17])[C@H:10]([CH2:11][CH:12]([CH3:13])[CH3:14])[NH:9][C:7](=[O:8])[CH:6]([CH2:5][S:4][C:1](=[O:3])[CH3:2])[CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

8

Reactant 5

HCID 6115AnilineHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 53805712N-(2-acetylthiomethyl-4-phenylbutanoyl)-(L)-leucine

Product 1

HCID 131720012N-(2-Acetylthiomethyl-4-phenylbutanoyl)-(L)-leucine, N-phenylamideYield 50%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-(2-acetylthiomethyl-4-phenylbutanoyl)-(L)-leucine (derived from the higher RfTLC fraction) (182 mg. 0.5 mmole) in 2 mL of THF at 0° C. was added aniline (93 mg, 1.0 mmole) and 1-hydroxybenzotriazole hydrate (HOBT·H2O, 101 mg, 0.75 mole) and N-methylmorpholine (202 mg, 2.0 mmole). The mixture was stirred at 0° C. for 15 minutes, then 192 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 1.0 mmole) was added and the mixture stirred overnight. The solution was worked up by adding 7 mL methylene chloride and the mixture extracted with 3×3 ml of 5% sodium bicarbonate, then 2×2 mL of brine. The organic layer was dried over MgSO4, filtered and the solvent removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluted with methylene chloride/ethyl acetate (90/10) to obtain 110 mg of product (yield =50%). By 1H-NMR, we see two rotomers present at room temperature.

Workup

  1. customat 0° C.
  2. stirringthe mixture stirred overnight
  3. extractionthe mixture extracted with 3×3 ml of 5% sodium bicarbonate
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluted with methylene chloride/ethyl acetate (90/10)

Sources & evidence

ORD record
ord-64da471676e444db85cead7096b3b298
Source dataset
uspto-grants-1997_05
Patent number
US05629343

Reaction notes

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