反应详情

A mixture of 5-fluoro-6-methoxypyridin-3-amine (3.34 g, 23.53 mmol) and (S)-4-(2-fluoro-5-((2-methyl-4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (13.6 g crude from previous step) in THF (150 mL) at −10° C. was treated dropwise with LiHMDS (1.0 M in THF, Aldrich; 64.2 mL, 64.2 mmol) and the mixture was stirred for 30 min. The reaction was quenched with water and saturated NH4Cl(aq) (100 mL each) and diluted with EtOAc (50 mL). The organic layer was separated, and precipitated solids were collected by filtration. The filtered organic layer was then concentrated to minimal volume, and the precipitated brownish-yellow solid was collected by filtration and washed with a minimal amount of EtOAc. All collected solids were then combined, slurried in isopropanol, collected by filtration, and dried in vacuo to give (S)-4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-((2-methyl-4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (9.678 g, 81% over 2 steps) as a yellow solid. m/z (ESI, +ve ion) 758 (M+H)+.

1. customThe reaction was quenched with water and saturated NH4Cl(aq) (100 mL each)
2. additiondiluted with EtOAc (50 mL)
3. customThe organic layer was separated
4. customprecipitated solids
5. filtrationwere collected by filtration
6. concentrationThe filtered organic layer was then concentrated to minimal volume
7. filtrationthe precipitated brownish-yellow solid was collected by filtration
8. washwashed with a minimal amount of EtOAc
9. customAll collected solids
10. filtrationcollected by filtration
11. customdried in vacuo