Diisopropylethylamine → (1-(3-(N-methyl-N-((1R)-1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)phenyl)ethyl)carbamic acid tert-butyl ester

HRID 366122Notes

Reaction equation

HRID 366122 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][CH:19]=1)[C:14]([OH:16])=O)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:42][N:43]([CH2:60][CH2:61][C:62]1[S:63][CH:64]=[CH:65][CH:66]=1)[C:44](=[O:59])[C@H:45]([NH:57][CH3:58])[CH2:46][C:47]1[CH:56]=[CH:55][C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:48]=1.C(N(C(C)C)C(C)C)C>ClCCl.CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([C:11]1[CH:19]=[CH:18][CH:17]=[C:13]([C:14](=[O:16])[N:57]([CH3:58])[C@@H:45]([C:44](=[O:59])[N:43]([CH3:42])[CH2:60][CH2:61][C:62]2[S:63][CH:64]=[CH:65][CH:66]=2)[CH2:46][C:47]2[CH:56]=[CH:55][C:54]3[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=3)[CH:48]=2)[CH:12]=1)[CH3:10])([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 223270393-(1-((tert-Butoxycarbonyl)amino)ethyl)benzoic acid

Product 1

HCID 54463719(1-(3-(N-methyl-N-((1R)-1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)phenyl)ethyl)carbamic acid tert-butyl esterYield 97.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

3-(1-(t-Butyloxycarbonylamino)ethyl)benzoic acid (217 mg, 0.82 mmol) was dissolved in dichloromethane (5 ml) and N,N-dimethylformamide (3 ml). 1-Hydroxy-7-azabenzotriazole (111 mg, 0.82 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (157 mg, 0.82 mmol) was added. A solution of (2R)-N-Methyl-2-(methylamino)-3-(2-naphthyl)-N-(2-(2-thienyl)ethyl)propionamide (288 mg, 0.82 mmol) in dichloromethane (3 ml) was added. Ethyldiisopropylamine (0.14 ml, 0.82 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 (80 ml) and washed with 10% sodium hydrogen sulfate solution (50 ml). The aqueous phase was extracted with ethyl acetate (2×40 ml). The combined organic layers were washed with sa sodium hydrogen carbonate solution (50 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silcia (110 g), using ethyl acetate/heptane 1:1 as eluent, to give 479 mg of (1-(3-(N-methyl-N-((1R)-1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)phenyl)ethyl)carbamic acid tert-butyl ester.

Workup

  1. temperaturewas warming up to room temperature
  2. washwashed with 10% sodium hydrogen sulfate solution (50 ml)
  3. extractionThe aqueous phase was extracted with ethyl acetate (2×40 ml)
  4. washThe combined organic layers were washed with sa sodium hydrogen carbonate solution (50 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 silcia (110 g)

Sources & evidence

ORD record
ord-5d5e2e958b934fbab14c4227890b9734
Source dataset
uspto-grants-2000_10
Patent number
US06127354

Reaction notes

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