Reaktion #45613

Reaktionsgleichung

2-tributylstannyl-1-methylpyrrole

6-Bromo-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile

→

2-cyclopropyl-7-fluoro-5-methyl-6-(1-methyl-1H-pyrrol-2-yl)-1,3-benzoxazole-4-carbonitrile

Ausbeute 79.0%

Lösungsmittel

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturby heating
2. 2
   Temperaturunder reflux for 19 hours under nitrogen atmosphere
3. 3
   SonstigeThe reaction liquid
4. 4
   Temperaturwas cooled
5. 5
   Sonstigethe insoluble matter was separated by filtration through Celite
6. 6
   Einengenthe solvent was concentrated under reduced pressure
7. 7
   Sonstigeby removing tin-
8. 8
   Waschenby elution with a mixed solvent of n-hexane/ethyl acetate (10:1

Vorschrift

6-Bromo-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-77) (200 mg, 0.68 mmol) was dissolved in toluene (4 ml), then 2-tributylstannyl-1-methylpyrrole (300 mg, 0.81 mmol) and 2,6-di-tert-butylcresol (2 mg) and bis(triphenylphosphine)palladium(II) dichloride (24 mg, 0.03 mmol) were added, followed by heating under reflux for 19 hours under nitrogen atmosphere. The reaction liquid was cooled, the insoluble matter was separated by filtration through Celite, the solvent was concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography, followed by removing tin-derived side products with n-hexane and by elution with a mixed solvent of n-hexane/ethyl acetate (10:1, v/v) to obtain 2-cyclopropyl-7-fluoro-5-methyl-6-(1-methyl-1H-pyrrol-2-yl)-1,3-benzoxazole-4-carbonitrile (158 mg, 79%) as a pale yellow transparent oily substance. Apart of this (157 mg, 0.53 mmol) was dissolved in dimethyl sulfoxide (3 ml), triethylamine (187 μl, 1.33 mmol) and (3S)-3-(dimethylamino)pyrrolidine (101 μl, 0.80 mmol) were added, followed by stirring at 90° C. under nitrogen atmosphere for 13 hours. After cooling to room temperature, ethyl acetate was added, followed by fractionation with water. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated away, the resulting residue was subjected to silica gel column chromatography and eluted with a mixed solvent of chloroform/methanol (20:1, v/v). The resulting residue was recrystallized and purified with a mixed solvent of diethyl ether-n to obtain the entitled compound (104 mg, 50%) as a white solid.

Quelle