Sodium hydride → 4-[4-(1-tert-butoxy carbonylamino-1-methylethyl)phenyl]-5-chloro-N-(4-(1-imidazolyl)-phenyl]pyrimidine-2-amine

HRID 1359451

Reaktionsgleichung

Reaktionsgleichung von HRID 1359451
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][C:11]([C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:25]([Cl:26])=[CH:24][N:23]=[C:22](Cl)[N:21]=2)=[CH:16][CH:15]=1)([CH3:13])[CH3:12])=[O:9])([CH3:6])([CH3:5])[CH3:4].[NH2:28][C:29]1[CH:34]=[CH:33][C:32]([N:35]2[CH:39]=[CH:38][N:37]=[CH:36]2)=[CH:31][CH:30]=1>C1COCC1>[C:3]([O:7][C:8]([NH:10][C:11]([C:14]1[CH:15]=[CH:16][C:17]([C:20]2[C:25]([Cl:26])=[CH:24][N:23]=[C:22]([NH:28][C:29]3[CH:30]=[CH:31][C:32]([N:35]4[CH:39]=[CH:38][N:37]=[CH:36]4)=[CH:33][CH:34]=3)[N:21]=2)=[CH:18][CH:19]=1)([CH3:13])[CH3:12])=[O:9])([CH3:6])([CH3:4])[CH3:5]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 3201654-(1H-imidazol-1-yl)anilineHCID 181832304-[4-(1-Tert-butoxycarbonylamino-1-methylethyl)phenyl]-2,5-dichloropyrimidine

Produkt 1

HCID 181832294-[4-(1-tert-butoxy carbonylamino-1-methylethyl)phenyl]-5-chloro-N-(4-(1-imidazolyl)-phenyl]pyrimidine-2-amineAusbeute 23,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Sodium hydride (330 mg, 8.25 mmol) was added to a solution of 4-[4-(1-tert-butoxycarbonylamino-1-methylethyl)phenyl]-2,5-dichloropyrimidine (1.0 g, 2.62 mmol) and 1-(4-aminophenyl)-1H-imidazole (438 mg, 2.75 mmol) in dry THF (40 ml) under N2 and the mixture heated to reflux for 3 h. The reaction was quenched with H2O (5 ml), diluted with brine (50 ml) and extracted with ethyl acetate (2×150 ml). The ethyl acetate extracts were dried (MgSO4), concentrated in vacuo and the residue purified by column chromatography (silica; 2% ethyl acetate in CH2Cl2) to give 4-[4-(1-tert-butoxy carbonylamino-1-methylethyl)phenyl]-5-chloro-N-[4-(1-imidazolyl)-phenyl]pyrimidine-2-amine as a yellow solid (310 mg) m.p. 218-220°. This intermediate was stirrd at room temperature in trifluoroacetic acid (4 ml) for 3 h before concentrating the reaction in vacuo. The residue was diluted with 2M NaOH (aq) (50 ml) and extracted with CH2Cl2-ethanol (20:1) (3×50 ml), the extracts dried (MgSO4) and concentrated in vacuo. Trituration of the resultant solid with diethylether-ethyl acetate (4:1) gave the title compound as a pale yellow solid (175 mg) m.p. 199-201°. δH (d6DMSO) 10.05 (1H, bs), 8.62 (1H, s),8.15 (1H, s), 7.88 (2H, d, J 7.9 Hz), 7.78 (2H, d, J 8.5 Hz), 7.69 (2H, d, J 8.5 Hz), 7.65 (1H, s), 7.55 (2H, d, J 8.8 Hz), 1.42 (6H, s). MS (ESI) 405 (MH+, 100%).

Aufarbeitung

  1. temperaturethe mixture heated
  2. temperatureto reflux for 3 h
  3. customThe reaction was quenched with H2O (5 ml)
  4. additiondiluted with brine (50 ml)
  5. extractionextracted with ethyl acetate (2×150 ml)
  6. dry with materialThe ethyl acetate extracts were dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customthe residue purified by column chromatography (silica; 2% ethyl acetate in CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-3c311eed910646ea9996b47dc921d1bd
Quelldatensatz
uspto-grants-2003_07
Patentnummer
US06600037B1

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