Diethyl Ether → (3S)-3-[(1-Methylindole-2-Carbonyl)Leucinyl]Amino4-Oxobutanoic Acid, t-Butyl Ester Semicarbazone

HRID 1531707Notes

Reaction equation

HRID 1531707 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:20]([NH:22][C@H:23]([CH:36]=[O:37])[CH2:24][C:25](=[N:31][NH:32][C:33]([NH2:35])=[O:34])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:21])[CH2:16][CH:17]([CH3:19])[CH3:18].CCN=C=NCCCN(C)C.CCOCC>C(Cl)Cl.CN(C1C=CN=CC=1)C>[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:20]([NH:22][C@H:23]([CH:36]=[O:37])[CH2:24][C:25](=[N:31][NH:32][C:33]([NH2:35])=[O:34])[O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:21])[CH2:16][CH:17]([CH3:18])[CH3:19])=[O:13]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 276951H-Indole-2-carboxylic acid, 1-methyl-HCID 865839973(S)-(Leucinyl)amino-4-oxobutanoic acid, t-butyl ester semicarbazone

Product 1

HCID 86583996(3S)-3-[(1-Methylindole-2-Carbonyl)Leucinyl]Amino4-Oxobutanoic Acid, t-Butyl Ester SemicarbazoneYield 80%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

1-Methylindole-2-carboxylic acid (70 mg, 0.4 mmol) and 3(S)-(Leucinyl)amino-4-oxobutanoic acid, t-butyl ester semicarbazone (131 mg, 0.4 mmol) were dissolved in methylene chloride (2 mL) and both DMAP (49 mg, 0.40 mmol) and EDAC (107 mg, 0.56 mmol) were added to the solution under a nitrogen atmosphere at 0° C. Stirring was continued for 1 hour at 0° C. and an additional 3 hours at room temperature. The reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution. The ethyl acetate solution was washed successively with 5% KHSO4 solution, saturated with sodium bicarbonate solution (2×) and brine, dried over sodium sulfate, and concentrated in vacuo to give a crude solid. Trituration of the solid with ether afforded the title product as a white powder (156 mg, 80%). TLC: (methanol/methylene chloride: 5/95, silica gel): Rf=0.42; 1H NMR (CDCl3+CD3OD): δ 8.18 (s, 1H), 7.66-7.11 (m, 6H), 6.97 (s, 1H), 6.32 (d, J=7.7, 1H), 4.95-4.88 (m, 1H), 4.70-4.62 (m, 1H), 4.03 (s, 3H), 2.82-2.56 (m, 2H), 1.87-1.58 (m, 3H), 1.38 (9H), 1.00 (t, J-6.3, 6H).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution
  2. washThe ethyl acetate solution was washed successively with 5% KHSO4 solution, saturated with sodium bicarbonate solution (2×) and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customto give a crude solid

Sources & evidence

ORD record
ord-89ae45d9d54844799511c22ba67b7628
Source dataset
uspto-grants-2001_03
Patent number
US06200969B1

Reaction notes

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