Sodium Chloride → N,N'-di-(4-chlorophenethyl)-2-((S)-2-(p-methoxybenzylmercapto)-3-phenylpropionylamino)malonamide

HRID 2269825Notes

Reaction equation

HRID 2269825 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][S:8][C@@H:9]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]([NH:12][CH:13]([C:17]([OH:19])=O)[C:14](O)=[O:15])=[O:11])=[CH:5][CH:4]=1.[Cl-:29].[Na+].[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][CH2:39][NH2:40])=[CH:34][CH:33]=1.C[N:42]1[CH2:47][CH2:46]OCC1.Cl.C(N=C=NCCCN(C)C)C.O.ON1[C:66]2[CH:67]=[CH:68][CH:69]=[CH:70][C:65]=2N=N1>C(OCC)(=O)C.CCCCCC.O1CCCC1.ClCCl>[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][CH2:39][NH:40][C:14](=[O:15])[CH:13]([NH:12][C:10](=[O:11])[C@@H:9]([S:8][CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:28][CH:27]=2)[CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:17]([NH:42][CH2:47][CH2:46][C:69]2[CH:70]=[CH:65][C:66]([Cl:29])=[CH:67][CH:68]=2)=[O:19])=[CH:34][CH:33]=1

Participants

10

Reactant 6

HCID 5234Sodium ChlorideHCID 79724-MethylmorpholineHCID 674302-(4-Chlorophenyl)ethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 540116352-((S)-2-(p-methoxybenzylmercapto)-3-phenylpropionylamino)malonic acid

Product 1

HCID 20713101N,N'-di-(4-chlorophenethyl)-2-((S)-2-(p-methoxybenzylmercapto)-3-phenylpropionylamino)malonamide

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent3×

Procedure

Combine 2-((S)-2-(p-methoxybenzylmercapto)-3-phenylpropionylamino)malonic acid (prepared by the method of Preparation 5, 0.476 g, 63% acid/37% sodium chloride, 0.74 mmol), dichloromethane (9 mL), and tetrahydrofuran (1.5 mL). Add 4-chlorophenylethylamine (0.31 mL, 2.23 mmol), N-methylmorpholine (0.25 mL, 2.3 mmol), 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloric acid salt (0.427 g, 2.23 mmol) and 1-hydroxybenztriazole hydrate (0.301 g, 2.23 mmol). After 3 days, concentrate in vacuo and partition the concentrated reaction mixture between an aqueous 5% sulfuric acid solution and ethyl acetate. Separate the layers and extract the organic layer with a saturated aqueous sodium bicarbonate solution and then brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with 2/3 ethyl acetate/hexane, 1/1 ethyl acetate/hexane, and then 1/2 ethyl acetate/hexane to give the title compound.

Workup

  1. concentrationconcentrate in vacuo
  2. custompartition
  3. customthe concentrated reaction mixture between an aqueous 5% sulfuric acid solution and ethyl acetate
  4. customSeparate the layers
  5. extractionextract the organic layer with a saturated aqueous sodium bicarbonate solution
  6. dry with materialDry the organic layer over Na2SO4
  7. filtrationfilter
  8. customevaporate in vacuo
  9. customto give a residue

Sources & evidence

ORD record
ord-79746f16f87d458890de72e8e4ac08d4
Source dataset
uspto-grants-2001_12
Patent number
US06329550B1

Reaction notes

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