6-Chloro-3-(3,3,4,4,4-pentafluorobutyl)imidazo[1,5-a]pyridine-1-carbonitrile → 6-Chloro-3-(3,3,4,4,4-pentafluorobutyl)imidazo[1,5-a]pyridine-1-carboximidamide

Temperature

100 °C

Trimethyl aluminum (2.0 M toluene, 10 mL, 20 mmol) was added to ammonium chloride (1.07 g, 20 mmol) suspended in toluene (30 mL) at 0° C. The solution was then stirred at room temperature for 2 hours to give a 0.5 M amino(chloro)methylaluminum solution in toluene. To the intermediate from Step I (2 g, 6.33 mmol) in toluene (1 mL) was added amino(chloro)methylaluminum (40 mL of 0.5 M solution in toluene, 20 mmol). The resulting mixture was left stirring at 100° C. for 18 hours. The reaction mixture was cooled to room temperature and quenched with silica-gel and 1:1 methanol-chloroform (50 mL). The resulting slurry was stirred vigorously for 30 minutes. The reaction mixture was filtered through a silca gel pad (1″) and washed with methanol. The filtrate was concentrated. The residue was suspended in water and extracted with 30% IPA/CHCl3 (3×). The organic layer was concentrated in vacuo to yield a brown solid. m/z=340.8 (M+1).

1. waitThe resulting mixture was left
2. temperatureThe reaction mixture was cooled to room temperature
3. customquenched with silica-gel and 1:1 methanol-chloroform (50 mL)
4. stirringThe resulting slurry was stirred vigorously for 30 minutes
5. filtrationThe reaction mixture was filtered through a silca gel pad (1″) and
6. washwashed with methanol
7. concentrationThe filtrate was concentrated
8. extractionextracted with 30% IPA/CHCl3 (3×)
9. concentrationThe organic layer was concentrated in vacuo
10. customto yield a brown solid

ORD record

ord-0016598916fd42a2a146352470e1a040

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365574B2