1H-Indole-2-carboxylic acid, 1-methyl- → N-[(1-methylindole-2-carbonyl)valinyl]-3-amino-4-hydroxy-5-fluoropentanoic Acid T-Butyl Ester

HRID 397457Notes

Reaction equation

HRID 397457 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:11]([OH:13])=O.[NH2:14][C@H:15]([C:19]([NH:21][CH:22]([CH:31]([OH:34])[CH2:32][F:33])[CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:20])[CH:16]([CH3:18])[CH3:17].Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:11]([NH:14][C@H:15]([C:19]([NH:21][CH:22]([CH:31]([OH:34])[CH2:32][F:33])[CH2:23][C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])=[O:20])[CH:16]([CH3:17])[CH3:18])=[O:13]

Participants

6

Reactant 3

HCID 276951H-Indole-2-carboxylic acid, 1-methyl-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86584005N-(valinyl)-3-amino-4-hydroxy-5-fluoropentanoic acid, t-butyl ester

Product 1

HCID 69986607N-[(1-methylindole-2-carbonyl)valinyl]-3-amino-4-hydroxy-5-fluoropentanoic Acid T-Butyl EsterYield 65%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-methylindole-2-carboxylic acid (130 mg, 0.74 mmol) and N-(valinyl)-3-amino-4-hydroxy-5-fluoropentanoic acid, tert-butyl ester in methylene chloride (5 mL) and cooled to 0° C. Solid 4-dimethylaminopyridine (DMAP) (95 mg, 0.78 mmol) and 1-(3′-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC) (200 mg, 1.04 mmol) were added to the solution at 0° C. The reaction mixture was stirred at 0° C. for 1 h and allowed to warm slowly to room temperature. After 4 h the reaction was partitioned between ethyl acetate (EtOAc) and 5% KHSO4 aqueous solution. The organic layer was washed with 5% KHSO4 solution, saturated sodium bicarbonate solution, brine, dried (Na2SO4) and concentrated to a foam. The crude residue was triturated with diethyl ether and the solid filtered to afford the title compound as a light brown solid (224 mg, 65% yield). TLC(MeOH:CH2Cl2, 1:9): Rf=0.46.

Workup

  1. temperatureto warm slowly to room temperature
  2. customAfter 4 h the reaction was partitioned between ethyl acetate (EtOAc) and 5% KHSO4 aqueous solution
  3. washThe organic layer was washed with 5% KHSO4 solution, saturated sodium bicarbonate solution, brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated to a foam
  6. customThe crude residue was triturated with diethyl ether
  7. filtrationthe solid filtered

Sources & evidence

ORD record
ord-c30d9507145d4c31a530059f84c7c876
Source dataset
uspto-grants-2003_08
Patent number
US06610683B2

Reaction notes

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