1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-[(1,3-Dimethylindole-2-Carbonyl)Valinyl]-3-Amino-4-Hydroxy-5-(2',6'-Dichlorobenzyloxy)Pentanoic Acid, t-Butyl Ester

HRID 1531715Notes

Reaction equation

HRID 1531715 reaction equation
O.ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.[CH3:23][N:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([CH3:33])=[C:25]1[C:34]([NH:36][C@H:37]([C:41]([OH:43])=O)[CH:38]([CH3:40])[CH3:39])=[O:35].[NH2:44][CH:45]([CH:54]([OH:66])[CH2:55][O:56][CH2:57][C:58]1[C:63]([Cl:64])=[CH:62][CH:61]=[CH:60][C:59]=1[Cl:65])[CH2:46][C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48]>C(OCC)(=O)C.CCCCCC.C(Cl)Cl>[CH3:23][N:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([CH3:33])=[C:25]1[C:34]([NH:36][C@H:37]([C:41]([NH:44][CH:45]([CH:54]([OH:66])[CH2:55][O:56][CH2:57][C:58]1[C:59]([Cl:65])=[CH:60][CH:61]=[CH:62][C:63]=1[Cl:64])[CH2:46][C:47]([O:49][C:50]([CH3:52])([CH3:51])[CH3:53])=[O:48])=[O:43])[CH:38]([CH3:39])[CH3:40])=[O:35]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 53637592N-(1,3-Dimethylindole-2-Carbonyl)ValineHCID 699869763-amino-5-(2',6'-dichlorobenzyloxy)-4-hydroxypentanoic Acid T-Butyl Ester

Product 1

HCID 86584002N-[(1,3-Dimethylindole-2-Carbonyl)Valinyl]-3-Amino-4-Hydroxy-5-(2',6'-Dichlorobenzyloxy)Pentanoic Acid, t-Butyl EsterYield 41%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
0 °C

Procedure

1-Hydroxybenzotriazole hydrate (153 mg, 1.0 mmol) and EDAC (268 mg, 1.4 mmol) were added to a methylene chloride solution of N-(1,3-dimethylindole-2-carbonyl)valine (288 mg, 1.0 mmol, in 3 mL of methylene chloride). The resultant mixture was stirred for 10 minutes under a nitrogen atmosphere at room temperature. A methylene chloride solution of 3-amino-5-(2′,6′-dichlorobenzyloxy)-4-hydroxypentanoic acid, t-butyl ester (364 mg, 1.0 mmol, in 2 mL of methylene chloride) was added to the reaction mixture and the mixture was first stirred for one hour under a nitrogen atmosphere at 0° C., and then for 16 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 crude product (583 mg). The crude product was subjected to flash chromatography on silica gel with ethyl acetate/hexane (2/3) to give the title product as a white solid (260 mg). TLC: (ethyl acetate/hexanes 1:1): Rf=0.38.

Workup

  1. waitfor 16 hours at room temperature
  2. customThe reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution
  3. extractionthe aqueous solution was back-extracted with ethyl acetate
  4. washThe combined ethyl acetate solutions were washed with 5% KHSO4 solution, saturated sodium bicarbonate solution (2×) and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customto give crude product (583 mg)

Sources & evidence

ORD record
ord-d6d9bd719f5641d3933b6a8d2e2fb1d5
Source dataset
uspto-grants-2001_03
Patent number
US06200969B1

Reaction notes

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