Water → N-Methyl-N-((1R)-1-(N-methyl-N-((1R)-1-(methylcarbamoyl)-2-(thiophen-2-yl)ethyl) carbamoyl)-2-(2-naphthyl)ethyl) carbamic acid tert butylester

HRID 1268637Notes

Reaction equation

HRID 1268637 reaction equation
C(OC([CH2:8][NH:9][CH:10]([CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=1)[C:11]([OH:13])=O)=O)(C)(C)C.ON1C2N=C[CH:33]=[CH:34][C:29]=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:47][NH:48][C:49](=[O:59])[C@H:50]([NH:57][CH3:58])[CH2:51][C:52]1[S:53][CH:54]=[CH:55][CH:56]=1.CN[C:62](=[O:72])C(NC)CC1SC=CC=1.[CH:73](NC(C)C)(C)C.[OH2:80]>C(Cl)Cl>[C:34]([O:80][C:62](=[O:72])[N:9]([CH3:8])[C@@H:10]([C:11](=[O:13])[N:57]([CH3:58])[C@@H:50]([C:49](=[O:59])[NH:48][CH3:47])[CH2:51][C:52]1[S:53][CH:54]=[CH:55][CH:56]=1)[CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=1)([CH3:33])([CH3:29])[CH3:73]

Participants

9

Reactant 7

HCID 962WaterHCID 7912DiisopropylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10535973(2R)-N-methyl-2-methylamino-3-(thiophen-2-yl)propionamideHCID 223270012-(Tert-butoxycarbonylmethylamino)-3-(2-naphthyl)propionic acidHCID 22327074N-Methyl-2-methylamino-3-(thiophen-2-yl)propionamide

Product 1

HCID 10767985N-Methyl-N-((1R)-1-(N-methyl-N-((1R)-1-(methylcarbamoyl)-2-(thiophen-2-yl)ethyl) carbamoyl)-2-(2-naphthyl)ethyl) carbamic acid tert butylester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

2-(tert Butoxycarbonylmethylamino)-3-(2-naphthyl)propionic acid (1.20 g; 3.55 mmol) was dissolved in methylene chloride (10 ml). 1-Hydroxy-7-azabenzotriazol (0.48 g ;3.55 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.75 g; 3.90 mmol) were added. The reaction mixture was stirred for 15 min at room temperature. 2R)-N-Methyl-2-methylamino-3-(thiophen-2-yl)propionamide (0.70 g; 3.55 mmol) was dissolved in methylene chloride (10 ml) and added. Diisopropylamine (0.61 ml; 3.55 mmol) was added. The reaction mixture was stirred at room temperature for 2 days. Methylene chloride (10 ml) and water (10 ml) were added to the reaction mixture. The phases were separated and the organic phase was washed with aqueous sodium hydrogensulfate (10%; 20 ml), saturated aqueous sodium hydrogencarbonate (20 ml). The organic phase was dried over magnesium sulfate and the solvent was removed in vacuo. The crude product was chromatographed on silica (2×20 cm) using ethylacetate/heptane (1:1) as eluent to afford 1.38 g of N-methyl-N-((1R)-1-(N-methyl-N-((1R)-1-(methylcarbamoyl)-2-(thiophen-2-yl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl) carbamic acid tert butylester.

Workup

  1. additionadded
  2. stirringThe reaction mixture was stirred at room temperature for 2 days
  3. customThe phases were separated
  4. washthe organic phase was washed with aqueous sodium hydrogensulfate (10%; 20 ml), saturated aqueous sodium hydrogencarbonate (20 ml)
  5. dry with materialThe organic phase was dried over magnesium sulfate
  6. customthe solvent was removed in vacuo
  7. customThe crude product was chromatographed on silica (2×20 cm)

Sources & evidence

ORD record
ord-8fe0851534f64c53be883483b7407daf
Source dataset
uspto-grants-2003_04
Patent number
US06555570B2

Reaction notes

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