反应详情

To a solution of 4-(5-chloro-2-methyl-phenyl)-pyridin-3-ylamine (500 mg, 2.29 mmol) in trimethyl orthoformate (1.94 g, 2.00 mL, 18.3 mmol, CAS RN 149-73-5) was added 2-3 drops of TFA. The reaction mixture was stirred at reflux for 2 hours and then concentrated under vacuum. The residue was dissolved in 5 ml toluene and evaporated (repeated 3 times). The residue was dissolved in THF (10 mL) and LiAlH4 (260 mg, 6.86 mmol) was added in portions at 0° C. The cooling bath was removed, the reaction mixture stirred at room temperature for 1 hour and then poured on 30 mL 10% aqueous NH4Cl solution and 30 mL EtOAc. The layers were separated and the aqueous layer extracted a second time with 30 mL EtOAc. The combined organic layers were washed with 30 mL brine, dried over MgSO4, filtered and concentrated under vacuum. The compound was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Light yellow solid (331 mg, 62%). MS (ESI): m/z=233.084 [M+H]+.

1. temperatureat reflux for 2 hours
2. concentrationconcentrated under vacuum
3. dissolutionThe residue was dissolved in 5 ml toluene
4. customevaporated (repeated 3 times)
5. dissolutionThe residue was dissolved in THF (10 mL)
6. customThe cooling bath was removed
7. stirringthe reaction mixture stirred at room temperature for 1 hour
8. additionpoured on 30 mL 10% aqueous NH4Cl solution and 30 mL EtOAc
9. customThe layers were separated
10. extractionthe aqueous layer extracted a second time with 30 mL EtOAc
11. washThe combined organic layers were washed with 30 mL brine
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated under vacuum
15. customThe compound was purified by silica gel chromatography
16. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)