Isoquinolin-3-Amine → 2,2-diethoxyethanimidamide

Temperature

70 °C

Shown in scheme O is the synthesis of intermediates compounds O-1 containing isoquinolin-3-amine. In a 250 ml of three-neck round bottom flask equipped with magnetic stir bar was charged the 2,2-diethoxyacetimidate (O-3) (6.7 g, 41.6 mmol) and MeOH (20 ml) then the phenyl methanamine hydrochloride (0.5 eq., 20.8 mmol) and MeONa (1 eq., 20.8 mmol) were added. The mixture was heated to 70° C. for 1 hr. The solution appeared dark. After the reaction finished, the MeOH solvent was removed by vacuum and the residue was dissolved in CH2Cl2 (100 ml). The organic phase washed with water (3×50 mL), then brine (1×30 mL). The organic layer was dried over magnesium sulfate, and filtered and the solvent reduced under vacuum. The product was purified by a silica gel column with 100% EA to give about 40.0% of desired product of 2,2-diethoxyacetamidine (O-2). The 2,2-diethoxyacetamidine (O-2) was dissolved in 6 ml of concentrated H2SO4 (99.9%) and the reaction was stirred at 40° C. for 72 hours. The solution was neutralized by 1M NaOH aqueous to PH 7.0. The crude was purified by silica gel column with 50:50 (petroleum ether: EA) to give final product O-1; yield from 13% to 70% depending on the substitution of phenyl methane amidine.

1. customthe synthesis of intermediates compounds
2. customIn a 250 ml of three-neck round bottom flask equipped with magnetic stir bar
3. customthe MeOH solvent was removed by vacuum
4. dissolutionthe residue was dissolved in CH2Cl2 (100 ml)
5. washThe organic phase washed with water (3×50 mL)
6. dry with materialThe organic layer was dried over magnesium sulfate
7. filtrationfiltered
8. customThe product was purified by a silica gel column with 100% EA

ORD record

ord-d43828e2cb034bcabc3668ce2c7c2519

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07998978B2