反应详情

According to Scheme 23, a mixture of 2-methyl-2,3-dihydro-4-(1H)-isoquinolone (630 mg, 3.9 mmol, Nichols, D. E. et al.; WO9706799), ammonium acetate (3.0 g, 39 mmol) and NaCNBH3 (491 mg, 7.8 mmol) in 25 mL of dry methanol was stirred for 2 days at RT. The solvent was removed and the residue was acidified to pH 2 to destroy the excess NaCNBH3. After basification with aq Na2CO3 to pH 10, the product was extracted into ether. The ether layer was dried (K2CO3) and the solvent was evaporated to provide 330 mg of the racemic 4-amino-2-methyltetrahydroisoquinoline. 1H NMR (CDCl3): δ 2.20 (bs, 2H, NH2), δ 2.60 (s, 3H, NCH3), δ 2.90 (d, 2H, CHCH2N), δ 3.55 (d, 1H, ArCH2N), δ 3.90 (d, 1H, ArCH2N), δ 4.15 (t, 1H, ArCHN), δ 7.20-7.60 (m, 4H, ArH).

1. customThe solvent was removed
2. customto destroy the excess NaCNBH3
3. extractionAfter basification with aq Na2CO3 to pH 10, the product was extracted into ether
4. dry with materialThe ether layer was dried (K2CO3)
5. customthe solvent was evaporated