Hydrochloric Acid → {1-[5-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-3-(2,2,2-trifluoro-ethyl)-imidazolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester

HRID 1185723Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1185723
CO[C:3]([CH:5]1[CH2:9][N:8]([CH2:10][C:11]([F:14])([F:13])[F:12])[CH2:7][N:6]1[C:15](=[O:25])[CH:16]([NH:20][C:21]([O:23][CH3:24])=[O:22])[CH:17]([CH3:19])[CH3:18])=[O:4].[Li+].[OH-].Cl.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[NH2:63][CH2:64][C:65]([C:67]1[CH:72]=[CH:71][C:70]([Br:73])=[CH:69][CH:68]=1)=[O:66]>C1COCC1.CO>[CH3:24][O:23][C:21](=[O:22])[NH:20][CH:16]([C:15]([N:6]1[CH:5]([C:3](=[O:4])[NH:63][CH2:64][C:65]([C:67]2[CH:72]=[CH:71][C:70]([Br:73])=[CH:69][CH:68]=2)=[O:66])[CH2:9][N:8]([CH2:10][C:11]([F:14])([F:12])[F:13])[CH2:7]1)=[O:25])[CH:17]([CH3:18])[CH3:19]

Komponenten

9

Edukt 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 27982162-Amino-1-(4-bromophenyl)ethan-1-one hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666201763-(2-Methoxycarbonylamino-3-methyl-butyryl)-1-(2,2,2-trifluoro-ethyl)-imidazolidine-4-carboxylic acid methyl ester

Produkt 1

HCID 66620808{1-[5-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-3-(2,2,2-trifluoro-ethyl)-imidazolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl esterAusbeute 104,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

3-(2-Methoxycarbonylamino-3-methyl-butyryl)-1-(2,2,2-trifluoro-ethyl)-imidazolidine-4-carboxylic acid methyl ester (95 mg, 0.257 mmol) was dissolved in THF (1.8 mL) and MeOH (0.9 mL). An aqueous solution of LiOH (10.8 mg, 0.208 mmol) was added and stirring at room temperature was continued. After the hydrolysis was complete, the reaction was neutralized with aqueous HCl (1M). The organic solvents were removed in vacuo and the aqueous suspension was frozen and lyophilized. The crude material was used in the next step without further purification. The crude material was dissolved in DMF (1.5 mL) and HATU (97.6 mg, 0.257 mmol) and DIEA (66.3 mg, 0.514 mmol) were added. The reaction was stirred at room temperature for five minutes, after which the amino-(4′bromo) acetophenone hydrochloride salt (64.2 mg, 0.257 mmol) was added. Stirring at room temperature was continued. After 60 minutes, all volatiles were removed in vacuo and the crude material was purified via silica gel chromatography (eluent: EtOAc/hexanes) to yield the slightly impure product {1-[5-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-3-(2,2,2-trifluoro-ethyl)-imidazolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (148 mg): LCMS-ESI+: calc'd for C21H26BrF3N4O5: 551.3 (M+). Found: 551.2/553.2 (M+).

Aufarbeitung

  1. customThe organic solvents were removed in vacuo
  2. temperaturethe aqueous suspension was frozen
  3. customThe crude material was used in the next step without further purification
  4. dissolutionThe crude material was dissolved in DMF (1.5 mL)
  5. stirringThe reaction was stirred at room temperature for five minutes
  6. stirringStirring at room temperature
  7. customall volatiles were removed in vacuo
  8. customthe crude material was purified via silica gel chromatography (eluent: EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-e916a022fed74fcea1ff83083af04e54
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08669234B2

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