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

HRID 366121Notes

Reaction equation

HRID 366121 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][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=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][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=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 10666252(2R)-N-methyl-2-methylamino-3-(2-naphthyl)-N-(3-phenylpropyl)propionamideHCID 10847814(2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic acid

Product 1

HCID 59965086((3E)-1,1-dimethyl-4-(N-methyl-N-((1R)-1-(N-methyl-N-(3-phenylpropyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)but-3-enyl)carbamic acid tert-butyl esterYield 72.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(2E)-5-(tert-Butoxycarbonylamino)-5-methylhex-2-enoic acid (405 mg, 1.66 mmol) was dissolved in N,N-dimethylformamide (4 ml) and dichloromethane (4 ml). 1-Hydroxy-7-azabenzotriazole (227 mg, 1.66 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (319 mg, 1.66 mmol) was added. The solution was stirred at 0° C. for 40 min. A solution of (2R)-N-methyl-2-methylamino-3-(2-naphthyl)-N-(3-phenylpropyl)propionamide (600 mg, 1.66 mmol) in dichloromethane (4 ml) was added. Ethyldiisopropylamine (0.29 m., 1.66 mmol) was added. The solution was stirred for 2 days, while it was slowly warming up to room temperature. The reaction mixture was diluted with ethyl acetate (100 ml) and washed with 1N hydrochloric acid (100 ml). The aqueous phase was extracted with ethyl acetate (2×50 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crued product was purified by flash chromatography on silica (180 g), using ethyl acetate/hepaten (1:1) as eluent to give 706 mg of ((3E)-1,1-dimethyl-4-(N-methyl-N-((1R)-1-(N-methyl-N-(3-phenylpropyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)but-3-enyl)carbamic acid tert-butyl ester.

Workup

  1. stirringThe solution was stirred for 2 days, while it
  2. temperaturewas slowly warming up to room temperature
  3. washwashed with 1N hydrochloric acid (100 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×50 ml)
  5. washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customThe crued product was purified by flash chromatography on silica (180 g)

Sources & evidence

ORD record
ord-aef25ca9d6334e65b10f46cd519638d1
Source dataset
uspto-grants-2000_10
Patent number
US06127354

Reaction notes

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