1-Naphthylglycine → (3S)-3-[N-((1-Naphthylamino)Acetyl)Leucinyl]Amino-4-Oxobutanoic Acid tert-Butyl Ester Semicarbazone

HRID 1066041Notes

Reaction equation

HRID 1066041 reaction equation
[C:1]1([NH:11][CH2:12][C:13]([OH:15])=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[C:16]([O:20][C:21](=[N:35][NH:36][C:37]([NH2:39])=[O:38])[CH2:22][C@H:23]([NH:26][C:27](=[O:34])[C@H:28]([CH2:30][CH:31]([CH3:33])[CH3:32])[NH2:29])[CH:24]=[O:25])([CH3:19])([CH3:18])[CH3:17].O.OC1C2N=NNC=2C=CC=1.Cl.C(N=C=NC(N)CC(C)C)C>CN1CCCC1=O.C(Cl)Cl>[C:16]([O:20][C:21](=[N:35][NH:36][C:37]([NH2:39])=[O:38])[CH2:22][C@H:23]([NH:26][C:27](=[O:34])[C@H:28]([CH2:30][CH:31]([CH3:33])[CH3:32])[NH:29][C:13](=[O:15])[CH2:12][NH:11][C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)[CH:24]=[O:25])([CH3:18])([CH3:19])[CH3:17]

Participants

7

Reactant 4

HCID 4587031-NaphthylglycineHCID 221346061-Ethyl-3-(3',3'-dimethyl-1'-aminopropyl)carbodiimide hydrochlorideHCID 865839973(S)-(Leucinyl)amino-4-oxobutanoic acid, t-butyl ester semicarbazoneHCID 178526939HCID 178526939, compound

Product 1

HCID 86585452(3S)-3-[N-((1-Naphthylamino)Acetyl)Leucinyl]Amino-4-Oxobutanoic Acid tert-Butyl Ester SemicarbazoneYield 100.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (1-naphthylamino)acetic acid (0.076 g, 0.38 mmol) and (3S)-3-(leucinyl)amino-4-oxobutanoic acid tert-butyl ester semicarbazone (see Example 1, Part B, 0.180 g, ca 0.41 mmol) in N-methylpyrrolidone(1.0 mL)-CH2Cl2(1.0 mL) at 0° C. (ice bath) under nitrogen was added hydroxybenzotriazole hydrate (0.075 g) followed by 1-ethyl-3-(3′,3′-dimethyl-1′-aminopropyl)carbodiimide hydrochloride (0.100 g, 0.52 mmol). After stirring at 0° C. for 3 hrs and at room temperature for 16 hrs, the mixture was partitioned between EtOAc-water. The organic phase was washed with water, 5% KHSO4, saturated NaHCO3 and saturated NaCl solutions, dried over anhydrous Na2SO4 and evaporated to dryness. The crude product was purified by flash chromatography eluting with MeOH—CH2Cl2 (1:30 then 1:15) to give the title compound (0.201 g, 100%) as a pale yellow foam. TLC(MeOH—CH2Cl2; 5:95) Rf=0.29.

Workup

  1. customthe mixture was partitioned between EtOAc-water
  2. washThe organic phase was washed with water, 5% KHSO4, saturated NaHCO3 and saturated NaCl solutions
  3. dry with materialdried over anhydrous Na2SO4
  4. customevaporated to dryness
  5. customThe crude product was purified by flash chromatography
  6. washeluting with MeOH—CH2Cl2 (1:30

Sources & evidence

ORD record
ord-5ede00294e1340808fded869007a60be
Source dataset
uspto-grants-2001_06
Patent number
US06242422B1

Reaction notes

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