Réaction #168422

Équation de réaction

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

Solvants

Dioxane

Conditions de réaction

Traitement

1. 1
   AutreA vial equipped with a stir bar
2. 2
   Autrethe mixture was degassed with N2
3. 3
   AutreThe vial was then sealed
4. 4
   TempératureThe 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
   Autrevial equipped with a stir bar
7. 7
   AutreThe reaction was degassed with N2 for 2 minutes
8. 8
   Autrethe vial was sealed
9. 9
   Températureheated at 110° C. for 20 hours
10. 10
    TempératureThe reaction was then cooled to room temperature
11. 11
    workup.ADDITIONdiluted with hexanes (2 mL) and CH2Cl2 (2 mL)
12. 12
    AutrePurification with 0 to 75% EtOAc/hexanes

Mode opératoire

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.

Source