反応 #168422

反応方程式

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

溶媒

Dioxane

反応条件

後処理

1. 1
   その他A vial equipped with a stir bar
2. 2
   その他the mixture was degassed with N2
3. 3
   その他The vial was then sealed
4. 4
   温度The 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
   その他vial equipped with a stir bar
7. 7
   その他The reaction was degassed with N2 for 2 minutes
8. 8
   その他the vial was sealed
9. 9
   温度heated at 110° C. for 20 hours
10. 10
    温度The reaction was then cooled to room temperature
11. 11
    workup.ADDITIONdiluted with hexanes (2 mL) and CH2Cl2 (2 mL)
12. 12
    その他Purification with 0 to 75% EtOAc/hexanes

実験手順

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.

出典