1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-[(1-methylindole-2-carbonyl)valinyl]-3-amino-4-hydroxy-5-fluoropentanoic Acid T-Butyl Ester

HRID 362491Notes

Reaction equation

HRID 362491 reaction equation
CCN=C=NCCCN(C)C.[CH3:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[C:14]1[C:22]([OH:24])=O.[NH2:25][C@H:26]([C:30]([NH:32][CH:33]([CH:42]([OH:45])[CH2:43][F:44])[CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[O:31])[CH:27]([CH3:29])[CH3:28]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[C:14]1[C:22]([NH:25][C@H:26]([C:30]([NH:32][CH:33]([CH:42]([OH:45])[CH2:43][F:44])[CH2:34][C:35]([O:37][C:38]([CH3:39])([CH3:40])[CH3:41])=[O:36])=[O:31])[CH:27]([CH3:28])[CH3:29])=[O:24]

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 276951H-Indole-2-carboxylic acid, 1-methyl-HCID 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 Ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

DMAP (95 mg, 0.78 mmol) and EDAC (200 mg, 1.04 mmol) were added as solid to a solution of 1-methylindole-2-carboxylic acid (130 mg, 0.74 mmol) and N-(valinyl)-3-amino-4-hydroxy-5-fluoropentanoic acid, t-butyl ester (227 mg, 0.74 mmol) in methylene chloride (5 mL), and the resultant solution was stirred for 1 hour under a nitrogen atmosphere at 0° C. and then 4 hours at room temperature. The reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution and the aqueous solution was back-extracted with ethyl acetate. The combined ethyl acetate solutions were washed with 5% KHSO4 solution, saturated sodium bicarbonate solution (2×) and brine, dried over sodium sulfate, and concentrated to give a foam. The foam was triturated with ether to yield the title product as a slightly brown solid (224 mg, 65%). TLC: (methanol/methylene chloride, 1:9): Rf =0.46.

Workup

  1. custom4 hours
  2. customat room temperature
  3. customThe reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution
  4. extractionthe aqueous solution was back-extracted with ethyl acetate
  5. washThe combined ethyl acetate solutions were washed with 5% KHSO4 solution, saturated sodium bicarbonate solution (2×) and brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customto give a foam
  9. customThe foam was triturated with ether

Sources & evidence

ORD record
ord-0c64a87e1671453595e47a49990c4c35
Source dataset
uspto-grants-1999_02
Patent number
US05869519

Reaction notes

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