반응 #168422
ord-a9812673d4c24bb4ac6c8d34feb97f52
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후처리
- 1기타A vial equipped with a stir bar
- 2기타the mixture was degassed with N2
- 3기타The vial was then sealed
- 4온도The catalyst slurry was then cooled back to room temperature
- 5workup.ADDITION1.5 mL of this catalyst slurry was added via syringe to a second
- 6기타vial equipped with a stir bar
- 7기타The reaction was degassed with N2 for 2 minutes
- 8기타the vial was sealed
- 9온도heated at 110° C. for 20 hours
- 10온도The reaction was then cooled to room temperature
- 11workup.ADDITIONdiluted with hexanes (2 mL) and CH2Cl2 (2 mL)
- 12기타Purification with 0 to 75% EtOAc/hexanes
실험 절차
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.