Phosgene → N-[4-fluoro-3-(trifluoromethyl)benzyl]-N'-(3-methyl-5-isoquinolinyl)urea

HRID 887280Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 887280
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11].[C:14](Cl)(Cl)=[O:15].CCN(C(C)C)C(C)C.[NH2:27][C:28]1[CH:37]=[CH:36][CH:35]=[C:34]2[C:29]=1[CH:30]=[C:31]([CH3:38])[N:32]=[CH:33]2>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH:7][C:14]([NH:27][C:28]2[CH:37]=[CH:36][CH:35]=[C:34]3[C:29]=2[CH:30]=[C:31]([CH3:38])[N:32]=[CH:33]3)=[O:15])=[CH:4][C:3]=1[C:10]([F:11])([F:12])[F:13]

Komponenten

6

Edukt 4

HCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 522270[4-Fluoro-3-(trifluoromethyl)phenyl]methanamineHCID 122120553-Methylisoquinolin-5-amine

Produkt 1

HCID 22032629N-[4-fluoro-3-(trifluoromethyl)benzyl]-N'-(3-methyl-5-isoquinolinyl)urea

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel2×

Versuchsvorschrift

4-Fluoro-3-(trifluoromethyl)benzylamine (0.8 g, 4.15 mmol) in toluene (20 mL) was refluxed with 20% w/v phosgene solution in toluene (2.1 mL) overnight. The mixture was cooled to room temperature and concentrated in vacuo. The residue was again taken up in toluene (25 mL) and was stirred overnight at 80° C. with DIEA (2 mL, 11.5 mmol) and 5-amino-3-methylisoquinoline (500 mg, 3.16 mmol). The mixture was cooled to room temperature, concentrated in vacuo, and the residue was purified by silica gel chromatography (97:3 CH2Cl2:CH3OH, eluant) to provide the title compound. The corresponding hydrochloride salt was prepared by treatment with methanolic HCl. 1H NMR (300 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.72 (s, 1H), 8.16 (d, 1H, J=7.8 Hz), 7.70-7.77 (m, 4H), 7.48-7.54 (m, 3H), 7.14 (t, 1H, J=5.9 Hz), 4.42 (d, 2H, J=6.1 Hz), 2.64 (s, 3H); MS (ESI+) m/z 378 (M+H).

Aufarbeitung

  1. concentrationconcentrated in vacuo
  2. temperatureThe mixture was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. customthe residue was purified by silica gel chromatography (97:3 CH2Cl2:CH3OH, eluant)

Quellen und Nachweise

ORD-Eintrag
ord-d91f034430704044967cb148c5eb9ae9
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08247413B2

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