反应详情

A mixture of 5-fluoro-6-methoxypyridin-3-amine (Anichem, N.J., USA, 100 mg, 0.704 mmol) and 4-(5-chloro-2-fluoropyridin-3-yl)-N-(2-methoxyethyl)-6-methyl-1,3,5-triazin-2-amine (130 mg, 0.437 mmol) in THF (5 mL) was cooled in an ice bath and LiHMDS (1.0 M, 1500 μL, 1.500 mmol) was added under nitrogen. After 5 min, the cooling bath was removed. After 10 min, the mixture was neutralized with HCl (5N, 0.3 mL) and then partitioned between EtOAc (20 mL) and water (10 mL). The organic layer was washed with water (5 mL). The combined aqueous layers were extracted with EtOAc (2×5 mL). The combined organic layers were dried over Na2SO4 and concentrated. The resulting solid was triturated with EtOAc (5 mL) and filtered. The yellow solid was rinsed with ether (2×3 mL) to give the desired product as a yellow powder (115 mg). LCMS (ES, pos.): calcd for C18H19ClFN7O2: 419.1. found: 420.2 (M+H)+. 1H NMR (400 MHz, d6-DMSO) mixture of rotamers δ 11.89, 11.67 (s, 1H); 8.73 (dd, J=6.75, 2.64 Hz, 1H); 8.14-8.58 (m, 4H); 3.94 (2s, 3H); 3.46-3.65 (m, 4H); 3.23, 3.29 (s, 3H); 2.46, 2.47 (s, 3H). 19F NMR (377 MHz, d6-DMSO) δ −139.65 (S); 139.26 (S).

1. temperaturewas cooled in an ice bath
2. customthe cooling bath was removed
3. waitAfter 10 min
4. custompartitioned between EtOAc (20 mL) and water (10 mL)
5. washThe organic layer was washed with water (5 mL)
6. extractionThe combined aqueous layers were extracted with EtOAc (2×5 mL)
7. dry with materialThe combined organic layers were dried over Na2SO4
8. concentrationconcentrated
9. customThe resulting solid was triturated with EtOAc (5 mL)
10. filtrationfiltered
11. washThe yellow solid was rinsed with ether (2×3 mL)