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Triethylamine → (3R*,4R*)-3-({Cyclopropyl-[2-(3-nitro-phenyl)-acetyl]-amino}-methyl)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158361
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1158361
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[N+:25]([C:28]1[CH:29]=[C:30]([CH2:34][C:35]([OH:37])=O)[CH:31]=[CH:32][CH:33]=1)([O-:27])=[O:26].[C:38]([O:42][C:43]([N:45]1[CH2:49][C@@H:48]([CH2:50][N:51]([CH:68]([CH3:70])[CH3:69])[C:52](=[O:67])[C:53]2[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[C:55]([O:61][CH2:62][CH2:63][CH2:64][O:65][CH3:66])[CH:54]=2)[C@H:47]([CH2:71][NH:72][CH:73]2[CH2:75][CH2:74]2)[CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CC#N>[C:38]([O:42][C:43]([N:45]1[CH2:49][C@@H:48]([CH2:50][N:51]([CH:68]([CH3:69])[CH3:70])[C:52](=[O:67])[C:53]2[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[C:55]([O:61][CH2:62][CH2:63][CH2:64][O:65][CH3:66])[CH:54]=2)[C@H:47]([CH2:71][N:72]([CH:73]2[CH2:74][CH2:75]2)[C:35](=[O:37])[CH2:34][C:30]2[CH:31]=[CH:32][CH:33]=[C:28]([N+:25]([O-:27])=[O:26])[CH:29]=2)[CH2:46]1)=[O:44])([CH3:40])([CH3:41])[CH3:39]
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Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 158763-Nitrophenylacetic acidHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68616408(3R*,4R*)-3-Cyclopropylaminomethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 68618278(3R*,4R*)-3-({Cyclopropyl-[2-(3-nitro-phenyl)-acetyl]-amino}-methyl)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel2×

Versuchsvorschrift

At 0° C. HBTU (426 mg, 1.12 mmol) is added to a solution of 3-nitrophenylacetic acid (187 mg, 1.03 mmol) in CH3CN (10 mL) and the resulting solution is stirred for 10 min. Then a solution of (3R*,4R*)-3-cyclopropylaminomethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.2 g, 0.375 mmol). (500 mg, 0.94 mmol) and triethylamine (1.04 mL, 7.5 mmol) in CH3CN (10 mL) is added at 0° C. and the reaction mixture is stirred at RT for another 2 h. For workup a sat. solution of NaHCO3 is added and the mixture is extracted with ethyl acetate. Washing of the combined extracts with brine, drying (Na2SO4), filtration and evaporation of the solvent affords the crude product which is purified by flash chromatography on silica gel (eluent: CH2Cl2 to CH2Cl2/MeOH 9:1) to give the title compound. MS (LC-MS): 597.0 [M+H-Boc]+; tR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mumin): 6.47 min.

Aufarbeitung

  1. customAt 0° C
  2. stirringthe reaction mixture is stirred at RT for another 2 h
  3. extractionthe mixture is extracted with ethyl acetate
  4. washWashing of the combined extracts with brine
  5. customdrying
  6. filtration(Na2SO4), filtration and evaporation of the solvent
  7. customaffords the crude product which
  8. customis purified by flash chromatography on silica gel (eluent: CH2Cl2 to CH2Cl2/MeOH 9:1)

Quellen und Nachweise

ORD-Eintrag
ord-a925cdd059e0493ca4e04e3ee1862e1c
Quelldatensatz
uspto-grants-2010_10
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07807709B2

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