Diisopropylethylamine → Ethyl (s)-3-((s)-2-(4,4-bis(trifluoromethyl)-3-(4-(3-(2-methylphenyl)ureido)-3-methoxybenzyl)-2,5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetylamino)-3-phenylpropionate

HRID 1840625

Reaktionsgleichung

Reaktionsgleichung von HRID 1840625
[B-](F)(F)(F)F.CCOC(C(C#N)=NOC(N(C)C)=[N+](C)C)=O.C(N(CC)C(C)C)(C)C.[F:32][C:33]([F:74])([F:73])[C:34]1([C:69]([F:72])([F:71])[F:70])[C:38](=[O:39])[N:37]([C@@H:40]([CH2:44][CH:45]([CH3:47])[CH3:46])[C:41](O)=[O:42])[C:36](=[O:48])[N:35]1[CH2:49][C:50]1[CH:55]=[CH:54][C:53]([NH:56][C:57]([NH:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=2[CH3:66])=[O:58])=[C:52]([O:67][CH3:68])[CH:51]=1.[NH2:75][C@H:76]([C:83]1[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=1)[CH2:77][C:78]([O:80][CH2:81][CH3:82])=[O:79]>CN(C=O)C>[F:72][C:69]([F:70])([F:71])[C:34]1([C:33]([F:74])([F:73])[F:32])[C:38](=[O:39])[N:37]([C@@H:40]([CH2:44][CH:45]([CH3:46])[CH3:47])[C:41]([NH:75][C@H:76]([C:83]2[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=2)[CH2:77][C:78]([O:80][CH2:81][CH3:82])=[O:79])=[O:42])[C:36](=[O:48])[N:35]1[CH2:49][C:50]1[CH:55]=[CH:54][C:53]([NH:56][C:57]([NH:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=2[CH3:66])=[O:58])=[C:52]([O:67][CH3:68])[CH:51]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 915085(S)-Ethyl 3-amino-3-phenylpropanoateHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 87951373(s)-2-(4,4-Bis(trifluoromethyl)-3-(4-(3-(2-methylphenyl)ureido)-3-methoxybenzyl)-2,5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetic acid

Produkt 1

HCID 91066696Ethyl (s)-3-((s)-2-(4,4-bis(trifluoromethyl)-3-(4-(3-(2-methylphenyl)ureido)-3-methoxybenzyl)-2,5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetylamino)-3-phenylpropionateAusbeute 71,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

1.89 g (5.77 mmol) of TOTU and 932 μL of N,N-diisopropylethylamine were added at 0° C. to a solution of 3.57 g (5.77 mmol) of (S)-2-(4,4-bis(trifluoromethyl)-3-(4-(3-(2-methylphenyl)ureido)-3-methoxybenzyl)-2, 5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetic acid (prepared from (S)-2-(4,4-bis(trifluoromethyl)-2,5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetic acid and 4-(3-(2-methylphenyl)ureido)-3-methoxybenzyl chloride as described in Example 18f) and 1.11 g (5.77 mmol) of ethyl (S)-3-amino-3-phenylpropionate in 30 mL of absolute DMF. After stirring at room temperature for 1 hour, DMF was removed in vacuo, the residue was taken up in ethyl acetate and the ethyl acetate solution was washed successively with an aqueous KHSO4K2SO4 solution, a saturated NaHCO3 solution and water. After drying the organic phase over sodium sulfate and filtering, the solvent was removed in vacuo and the residue was chromatographed over silica gel using ethyl acetate/heptane (2/3). After concentration of the product fractions, 3.26 g (71%) of the title compound were obtained.

Aufarbeitung

  1. customDMF was removed in vacuo
  2. washthe ethyl acetate solution was washed successively with an aqueous KHSO4K2SO4 solution
  3. dry with materialAfter drying the organic phase over sodium sulfate
  4. filtrationfiltering
  5. customthe solvent was removed in vacuo
  6. customthe residue was chromatographed over silica gel

Quellen und Nachweise

ORD-Eintrag
ord-9df09ac466a34b57b17d0a07ae4c3dd5
Quelldatensatz
uspto-grants-2004_01
Patentnummer
US06680333B2

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