ethyl 2-(4,6,7-trifluoro-1H-benzoimidazol-2-yl)propionate → ethyl 2-(2-{2-[1-(4,6,7-trifluoro-1H-benzoimidazol-2-yl)ethyl]-3-methyl-3H-benzoimidazol-5-carbonylamino}ethoxy}benzoate

HRID 412729Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 412729
[F:1][C:2]1[C:10]2[N:9]=[C:8]([CH:11]([CH3:17])[C:12](OCC)=O)[NH:7][C:6]=2[C:5]([F:18])=[C:4]([F:19])[CH:3]=1.[NH2:20][C:21]1[CH:43]=[CH:42][C:24]([C:25]([NH:27][CH2:28][CH2:29][O:30][C:31]2[CH:41]=[CH:40][CH:39]=[CH:38][C:32]=2[C:33]([O:35][CH2:36][CH3:37])=[O:34])=[O:26])=[CH:23][C:22]=1[NH:44][CH3:45]>CN1C(=O)N(C)CCC1>[F:1][C:2]1[C:10]2[N:9]=[C:8]([CH:11]([C:12]3[N:44]([CH3:45])[C:22]4[CH:23]=[C:24]([C:25]([NH:27][CH2:28][CH2:29][O:30][C:31]5[CH:41]=[CH:40][CH:39]=[CH:38][C:32]=5[C:33]([O:35][CH2:36][CH3:37])=[O:34])=[O:26])[CH:42]=[CH:43][C:21]=4[N:20]=3)[CH3:17])[NH:7][C:6]=2[C:5]([F:18])=[C:4]([F:19])[CH:3]=1

Komponenten

4

Edukt 2

HCID 18537794ethyl 2-(4,6,7-trifluoro-1H-benzoimidazol-2-yl)propionateHCID 18537992Ethyl 2-[2-(4-amino-3-methylaminobenzoylamino)ethoxy]benzoate

Produkt 1

HCID 18537795ethyl 2-(2-{2-[1-(4,6,7-trifluoro-1H-benzoimidazol-2-yl)ethyl]-3-methyl-3H-benzoimidazol-5-carbonylamino}ethoxy}benzoateAusbeute 49 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Lösungsmittel

Reaktionsbedingungen

Temperatur
195 °C

Versuchsvorschrift

Ethyl 2-(4,6,7-trifluoro-1H-benzoimidazol-2-yl)propionate (988 mg, 3.63 mmol) and ethyl 2-[2-(4-amino-3-methylaminobenzoylamino)ethoxy]benzoate (1.3 g, 3.63 mmol) were combined and placed under vacuum for 4 hours and then further combined with DMPU (4 ml). The mixture was stirred until in solution, evacuated overnight under high vacuum to remove residual gases, heated to 195° C. under a nitrogen stream for 4 hours, cooled to room temperature and partitioned between ethyl acetate and water. The organic layer was separated and washed with brine, dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica (stepwise gradient of 100% hexane to 100% ethyl acetate) and further purified by crystallization from MeOH/THF/water to provide ethyl 2-(2-{2-[1-(4,6,7-trifluoro-1H-benzoimidazol-2-yl)ethyl]-3-methyl-3H-benzoimidazol-5-carbonylamino}ethoxy}benzoate (1.0 g, 49%) as a white crystalline solid:

Aufarbeitung

  1. customevacuated overnight under high vacuum
  2. customto remove residual gases
  3. temperaturecooled to room temperature
  4. custompartitioned between ethyl acetate and water
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica (stepwise gradient of 100% hexane to 100% ethyl acetate) and
  10. customfurther purified by crystallization from MeOH/THF/water

Quellen und Nachweise

ORD-Eintrag
ord-99b895b1d69643d581a6e128ad22344b
Quelldatensatz
uspto-grants-2003_05
Patentnummer
US06562854B2

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