Reaktion #168422

Reaktionsgleichung

4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile

2-bromo-4-isopropylpyridine

cesium fluoride

pivalic acid

di(1-adamantyl)-n-butylphosphine

→

4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[4-(propan-2-yl)pyridin-2-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile

Lösungsmittel

Dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA vial equipped with a stir bar
2. 2
   Sonstigethe mixture was degassed with N2
3. 3
   SonstigeThe vial was then sealed
4. 4
   TemperaturThe catalyst slurry was then cooled back to room temperature
5. 5
   workup.ADDITION1.5 mL of this catalyst slurry was added via syringe to a second
6. 6
   Sonstigevial equipped with a stir bar
7. 7
   SonstigeThe reaction was degassed with N2 for 2 minutes
8. 8
   Sonstigethe vial was sealed
9. 9
   Temperaturheated at 110° C. for 20 hours
10. 10
    TemperaturThe reaction was then cooled to room temperature
11. 11
    workup.ADDITIONdiluted with hexanes (2 mL) and CH2Cl2 (2 mL)
12. 12
    SonstigePurification with 0 to 75% EtOAc/hexanes

Vorschrift

A vial equipped with a stir bar was charged with di(1-adamantyl)-n-butylphosphine (cataCXium A, Strem) (143.2 mg, 0.40 mmol) and palladium acetate (45 mg, 0.20 mmol). Dioxane (2.5 mL) was added, and the mixture was degassed with N2. The vial was then sealed and heated at 50° C. for 30 minutes. The catalyst slurry was then cooled back to room temperature, and 1.5 mL of this catalyst slurry was added via syringe to a second vial equipped with a stir bar and containing 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Preparative Example 3.1, Step 2;100 mg, 0.273 mmol), 2-bromo-4-isopropylpyridine (109 mg, 0.547 mmol; purchased from Combiphos), cesium fluoride (125 mg, 0.82 mmol), and pivalic acid (36.3 mg, 0.355 mmol). The reaction was degassed with N2 for 2 minutes, and then the vial was sealed and heated at 110° C. for 20 hours. The reaction was then cooled to room temperature, diluted with hexanes (2 mL) and CH2Cl2 (2 mL), and loaded directly onto a silica gel column. Purification with 0 to 75% EtOAc/hexanes afforded 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[4-(propan-2-yl)pyridin-2-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd for C28H29ClN6 [M+H]+=485. found=485.

Quelle