Diisopropylethylamine → N-methyl-N-((1R)-1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl ester

HRID 582404

Reaction equation

HRID 582404 reaction equation
[C:1]([O:5][C:6]([N:8]([C@H: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)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:47][NH:48][CH2:49][CH2:50][C:51]1[S:52][CH:53]=[CH:54][CH:55]=1.C(N(C(C)C)C(C)C)C>CN(C)C=O.ClCCl.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[N:8]([CH3:9])[C@@H:10]([C:11](=[O:13])[N:48]([CH3:47])[CH2:49][CH2:50][C:51]1[S:52][CH:53]=[CH:54][CH:55]=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)([CH3:3])([CH3:2])[CH3:4]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 436154N-Methyl-2-(thiophen-2-yl)ethan-1-amineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10065151(2R)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-naphthalen-2-ylpropanoic acid

Product 1

HCID 54259442N-methyl-N-((1R)-1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

##STR110## (2R)-2-(N-(tert-Butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)propionic acid (4.52 g, 13.7 mmol) was dissolved in N,N-dimethylformamide (6 ml) and dichloromethane (6 ml). 1-Hydroxy-7-azabenzotriazole (1.86 g, 13.7 mmol) was added as a solid. The solution was cooled to 0° C. N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (2.63 g, 13.7 mmol) was added. The solution was stirred for 15 min at 0° C. A solution of N-methyl-N-(2-(2-thienyl)ethyl)amine in dichloromethane (6 ml) was added. Ethyldiisopropylamine (2.37 ml, 13.7 mmol) was added. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (200 ml). The mixture was washed with 1N hydrochloric acid (150 ml) and saturated sodium hydrogen carbonate solution (150 ml). It was dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silcia (100 g), using ethyl acetate/heptane (1:2) as eluent to give 5.57 g of N-methyl-N-((1R)-1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl ester.

Workup

  1. stirringThe reaction mixture was stirred for 16 h, while it
  2. temperaturewas warming up to room temperature
  3. washThe mixture was washed with 1N hydrochloric acid (150 ml) and saturated sodium hydrogen carbonate solution (150 ml)
  4. dry with materialIt was dried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customThe crude product was purified by flash chromatography on silcia (100 g)

Sources & evidence

ORD record
ord-b0054d1c18c04421a577a593fc20dad3
Source dataset
uspto-grants-1999_07
Patent number
US05922770

Linked notes

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