Diisopropylethylamine → (3E)-1,1-dimethyl-4-(N-methyl-N-((1R)-1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)but-3-enylcarbamic acid tert-butyl ester

HRID 582406Notes

Reaction equation

HRID 582406 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:17])([CH3:16])[CH2:10]/[CH:11]=[CH:12]/[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:40][N:41]([CH2:58][CH2:59][C:60]1[S:61][CH:62]=[CH:63][CH:64]=1)[C:42](=[O:57])[C@H:43]([NH:55][CH3:56])[CH2:44][C:45]1[CH:54]=[CH:53][C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[CH:46]=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])[NH:8][C:9]([CH3:17])([CH3:16])[CH2:10]/[CH:11]=[CH:12]/[C:13](=[O:15])[N:55]([CH3:56])[C@@H:43]([C:42](=[O:57])[N:41]([CH3:40])[CH2:58][CH2:59][C:60]1[S:61][CH:62]=[CH:63][CH:64]=1)[CH2:44][C:45]1[CH:54]=[CH:53][C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[CH:46]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10831847(2R)-N-methyl-2-(methylamino)3-(2-naphthyl)-N-(2-(2-thienyl)ethyl)propionamideHCID 10847814(2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic acid

Product 1

HCID 59965083(3E)-1,1-dimethyl-4-(N-methyl-N-((1R)-1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)but-3-enylcarbamic acid tert-butyl esterYield 82.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(2E)-5-tert-Butoxycarbonylamino-5-methylhex-2-enoic acid (380 mg, 1.56 mmol) was dissolved in N,N-dimethylformamide (2 ml) and dichloromethane (2 ml). 1-Hydroxy-7-azabenzotriazole (299 mg, 1.56 mmol) was added as a solid. The solution was cooled to 0° C. N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (380 mg, 1.56 mmol) was added. The solution was stirred for 15 min. at 0° C. A solution of (2R)-N-methyl-2-(methylamino)-3-(2-naphthyl)-N-(2-(2-thienyl)ethyl)propionamide (500 mg, 1.42 mmol) in dichloromethane (2 ml) was added. Ethyldiisopropylamine (0.25 ml, 1.42 mmol) was added. The solution was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (70 ml) and washed with 1N hydrochloric acid (100 ml). The organic layer was washed with saturated sodium hydrogen carbonate solution (100 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (150 g), using ethyl acetate/heptane (1:1) as eluent, to give 679 mg of (3E)-1,1-dimethyl4-(N-methyl-N-((1R)-1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)but-3-enylcarbamic acid tert-butyl ester.

Workup

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

Sources & evidence

ORD record
ord-39f1a0b0ad5c4c85948f0b8d83d3dcc8
Source dataset
uspto-grants-1999_07
Patent number
US05922770

Reaction notes

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