2-Aminopyridine → 3-Chloro-1-methoxyisoquinoline

Temperature

125 °C

Into a sealed tube were added 1,3-dichloroisoquinoline (501 mg, 2.45 mmol), 2-aminopyridine (31 mg, 0.33 mmol), cuprous monochloride (37.2 mg, 0.162 mmol), MeONa (824 mg, 5.92 mmol), MeOH (3 ml) and diglyne (8 ml). The tube was sealed, evacuated and filled with N2 three times. The combined mixture was heated at 125° C. for 3 days under an atmosphere of nitrogen. After that time, the mixture was treated with water (20 ml) and extracted with EtOAc (3×50 ml). The organic extracts were washed with water (3×30 ml), brine (30 ml), dried over MgSO4, filtered, and concentrated in vacuo to give the title compound as light-yellow solid. 1H NMR (400 MHz, CDCl3): δ=4.15 (s, 3H), 7.26 (d, J=0.6 Hz, 1H), 7.51 (ddd, J=3.6, 4.6, 8.2 Hz, 1H), 7.64-7.69 (m, 2H), 8.20 (dd, J=8.4, 1.2 Hz, 1H). MS(ES+): m/z=194.08/196.01 (80/28) [MH+]. HPLC: tR=4.00 min (polar—5 min, ZQ3).

1. customThe tube was sealed
2. customevacuated
3. additionfilled with N2 three times
4. additionAfter that time, the mixture was treated with water (20 ml)
5. extractionextracted with EtOAc (3×50 ml)
6. washThe organic extracts were washed with water (3×30 ml), brine (30 ml)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORD record

ord-bfc3111864514da5b3b2d3bdcee55e72

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08178668B2