反応 #168465

反応方程式

4,6-dichloro-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine

cyclobutylmethanol

Cs2CO3

BINAP

→

6-chloro-4-(cyclobutylmethoxy)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine

溶媒

DMSO

反応条件

後処理

1. 1
   その他The reaction mixture was deoxygenated
2. 2
   その他by purging with nitrogen for 10 minutes
3. 3
   その他The reaction was again deoxygenated for 5 minutes
4. 4
   その他by purging with nitrogen
5. 5
   その他The reaction flask was sealed
6. 6
   温度The reaction mixture was then cooled
7. 7
   workup.ADDITIONdiluted with water (30 ml) and EtOAc (60 mL)
8. 8
   その他the organic layer was separated
9. 9
   洗浄The organic layer was washed with water (2×10 mL)
10. 10
    乾燥The organic layer was dried over anhydrous Na2SO4
11. 11
    ろ過filtered
12. 12
    濃縮concentrated
13. 13
    その他The residue was purified on a silica gel column (30% EtOAc/petroleum ether)

実験手順

To a solution of 4,6-dichloro-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine (Example 2.1, Step 2; 400 mg, 0.87 mmol) in DMSO (5 mL) was added cyclobutylmethanol (337 mg, 3.92 mmol), Cs2CO3 (848 mg, 2.61 mmol) and BINAP (108 mg, 0.17 mmol). The reaction mixture was deoxygenated by purging with nitrogen for 10 minutes and then Pd2dba3 (159 mg, 0.17 mmol) was added. The reaction was again deoxygenated for 5 minutes by purging with nitrogen. The reaction flask was sealed, and the mixture was heated at 100° C. for 16 h. The reaction mixture was then cooled, diluted with water (30 ml) and EtOAc (60 mL), and the organic layer was separated. The organic layer was washed with water (2×10 mL), followed by saturated brine (2×30 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified on a silica gel column (30% EtOAc/petroleum ether) to yield 6-chloro-4-(cyclobutylmethoxy)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine. MS ES/APCl calc'd. for C29H37ClN4O2 [M+H]+ 509. found 509.

出典