Citric Acid → HCID 9913922, compound

HRID 2297730Notes

Reaction equation

HRID 2297730 reaction equation
[C:1]([CH:4]([CH2:27][S:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:5][N:6]([CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[C:7](=[O:21])[NH:8][C@@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:10]([NH:12][CH3:13])=[O:11])([OH:3])=O.[OH:35][N:36]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1.[Cl-].O[NH3+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl.CN(C)C=O>[OH:35][NH:36][C:1]([CH:4]([CH2:27][S:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[CH2:5][N:6]([CH2:22][CH2:23][CH:24]([CH3:25])[CH3:26])[C:7](=[O:21])[NH:8][C@@H:9]([CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C:10]([NH:12][CH3:13])=[O:11])=[O:3]

Participants

9

Reactant 6

HCID 311Citric AcidHCID 79724-Methylmorpholine2×HCID 21645Hydroxylamine HClHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69931298HCID 69931298, compound

Product 1

HCID 9913922HCID 9913922, compoundYield 55.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

In anhydrous methylene chloride (4 ml) are dissolved (2S)-2-[3-[(2RS)-2-carboxy-3-(phenylthio)propyl]-3-isoamylureido]-N-methyl-3-phenylpropionamide (Compound No. 36-2, 100 mg), 1-hydroxybenzotriazole (68 mg) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (96 mg) under a nitrogen atmosphere. Then, N-methylmorpholine (0.05 ml) is added to the solution under ice cooling, and the mixture is stirred for 30 minutes. Next, to the mixture is added a solution containing hydroxylammonium chloride (52 mg) and N-methylmorpholine (0.08 ml) in dimethylformamide (1 ml), and the mixture is stirred under ice cooling for 10 minutes and then at room temperature overnight. A 5% aqueous citric acid solution is added to the reaction mixture, and the whole is extracted with ethyl acetate. The organic layer is washed with a 5% aqueous sodium hydrogencarbonate solution and saturated brine successively, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting oily matter is purified by silica gel column chromatography to give 57 mg (54%) of the titled compound (Compound No. 40-1) as noncrystalline powder.

Workup

  1. additionNext, to the mixture is added a solution
  2. stirringthe mixture is stirred under ice cooling for 10 minutes
  3. customat room temperature
  4. customovernight
  5. extractionthe whole is extracted with ethyl acetate
  6. washThe organic layer is washed with a 5% aqueous sodium hydrogencarbonate solution and saturated brine successively
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting oily matter is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a0d3dffeb0c2436b8ff2a52c184701dd
Source dataset
uspto-grants-2002_12
Patent number
US06492370B1

Reaction notes

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