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Urea → N-(6-Fluoro-1H-indazol-5-yl)-4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxamide

HRID 227718
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 227718
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][C:3]=1[NH2:11].[CH2:12]=[C:13]1[O:17][C:15](=O)[CH2:14]1.[F:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=1.[NH2:27][C:28]([NH2:30])=[O:29].[O-]S(C(F)(F)F)(=O)=O.[Yb+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>CC#N.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][C:3]=1[NH:11][C:15]([C:14]1[CH:23]([C:22]2[CH:25]=[CH:26][C:19]([F:18])=[CH:20][CH:21]=2)[NH:27][C:28](=[O:29])[NH:30][C:13]=1[CH3:12])=[O:17]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 5

HCID 1176UreaHCID 12661DiketeneHCID 680234-FluorobenzaldehydeHCID 2733225Ytterbium triflateHCID 450905046-fluoro-1H-indazol-5-amine

Produkt 1

HCID 57755913N-(6-Fluoro-1H-indazol-5-yl)-4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxamide
Ausbeute 3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

The product of Step (d) (41.0 mg, 0.276 mmol, 1.0 equiv) was dissolved in CH3CN (1 mL) and diketene (0.021 mL, 0.276 mmol, 1.0 equiv) was added. The reaction was heated to 80° C. for 2 hours, then cooled to room temperature and concentrated. The residue was dissolved in CH3CN (1 mL). 4-Fluorobenzaldehyde (0.030 mL, 0.276 mmol, 1.00 equiv), urea (25 mg, 0.41 mmol, 1.5 equiv), and ytterbium triflate (17 mg, 0.028 mmol, 0.10 equiv) and heated to 80° C. for 3 hours. The reaction was cooled to room temperature and water was added. The precipitate was collected by filtration and washed alternately with CH3CN and Et2O. The residue was purified by reverse phase HPLC (740% CH3CN/5 mM NH4HCO3, 19×50 mm Xterra Prep MS over 8 min) to provide 3 mg (3%) of the title compound. MS (ES+) m/e 384 [M+H].

Aufarbeitung

  1. temperaturecooled to room temperature
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in CH3CN (1 mL)
  4. temperatureThe reaction was cooled to room temperature
  5. filtrationThe precipitate was collected by filtration
  6. washwashed alternately with CH3CN and Et2O
  7. customThe residue was purified by reverse phase HPLC (740% CH3CN/5 mM NH4HCO3, 19×50 mm Xterra Prep MS over 8 min)

Quellen und Nachweise

ORD-Eintrag
ord-5511ecf4142c4108b0f328f25724d995
Quelldatensatz
uspto-grants-2009_07
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07560467B2

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