1-Hydroxybenzotriazole → (2-(4-hydroxy-2,6-dimethyl-phenyl)-1-{isopropyl-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-carbamoyl}-ethyl)-carbamic acid tert-butyl ester

HRID 1913554Notes

Reaction equation

HRID 1913554 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:13][C:14]1[C:19]([CH3:20])=[CH:18][C:17]([OH:21])=[CH:16][C:15]=1[CH3:22])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:23]([NH:26][CH:27]([C:29]1[NH:30][CH:31]=[C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[N:33]=1)[CH3:28])([CH3:25])[CH3:24].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([C:10](=[O:12])[N:26]([CH:23]([CH3:25])[CH3:24])[CH:27]([C:29]1[NH:30][CH:31]=[C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[N:33]=1)[CH3:28])[CH2:13][C:14]1[C:19]([CH3:20])=[CH:18][C:17]([OH:21])=[CH:16][C:15]=1[CH3:22])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 13656656Boc-L-2,6-DimethyltyrosineHCID 178457142HCID 178457142, compound

Product 1

HCID 178429012(2-(4-hydroxy-2,6-dimethyl-phenyl)-1-{isopropyl-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-carbamoyl}-ethyl)-carbamic acid tert-butyl esterYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a solution of 2-tert-Butoxycarbonylamino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionic acid (0.18 g, 0.6 mmol) in DMF (7 mL) was added isopropyl-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amine (0.11 g, 0.5 mmol), 1-hydroxybenzotriazole (0.22 g, 1.6 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.12 g, 0.6 mmol). The resulting mixture was stirred under an Argon atmosphere at rt overnight. The reaction mixture was extracted with EtOAc and the combined organic extracts were washed sequentially with saturated aqueous NaHCO3 solution, 1N HCl, saturated aqueous NaHCO3 solution, and brine. The organic phase was then dried over MgSO4, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by flash column chromatography (eluent: EtOAc) to afford the product (2-(4-hydroxy-2,6-dimethyl-phenyl)-1-{isopropyl-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-carbamoyl}-ethyl)-carbamic acid tert-butyl ester (0.13 g, 50%). MS (ES+): 521.5 (100%).

Workup

  1. extractionThe reaction mixture was extracted with EtOAc
  2. washthe combined organic extracts were washed sequentially with saturated aqueous NaHCO3 solution, 1N HCl, saturated aqueous NaHCO3 solution, and brine
  3. dry with materialThe organic phase was then dried over MgSO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by flash column chromatography (eluent: EtOAc)

Sources & evidence

ORD record
ord-e86fa6e7fc4c4713bc7b8af37f471d8b
Source dataset
uspto-grants-2013_12
Patent number
US08609709B2

Reaction notes

Loading…