反应详情

温度

85 °C

To a solution of (S)-methyl 4-((Z)—((R)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-ylidene)aminooxy)-2-(tert-butyldimethylsilyloxy)butanoate (91 g, 244 mg, 0.41 mmol) in DMA was added 6-methoxypyridine-2-boronic acid N-phenyldiethanolamine ester (488 mg, 1.64 mmol), Pd(dppf)2Cl2 (66 mg, 0.08 mmol), and 2 N Na2CO3 (2 mL, 4.1 mmol). The resultant mixture was degassed with N2 for 5 min then heated in a sealed tube at 85° C. for 14 h. The reaction was allowed to cool to r.t. and filtered through a pad of Celite topped with anhydrous Na2SO4, rinsing with EtOAc and CH3OH. The filtrate was concentrated to provide a black residue which was purified by preparative HPLC eluting with TFA/ACN/H2O. The fractions were dried down in vacuo to yield (S)-methyl 4-((Z)—((R)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-ylidene)aminooxy)-2-(tert-butyldimethylsilyloxy)butanoate. This material was directly taken up in dioxane (700 μL) and treated with 1:9 TFA:H2O (1 mL) for 3 h. The solvents were removed in vacuo to yield (S)-methyl 4-((Z)—((R)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-ylidene)aminooxy)-2-hydroxybutanoate (91h, 15 mg, 0.03 mmol). [M+H] calc'd for C25H27FN6O5, 511; found, 511.

1. customThe resultant mixture was degassed with N2 for 5 min
2. temperatureto cool to r.t.
3. filtrationfiltered through a pad of Celite
4. washrinsing with EtOAc and CH3OH
5. concentrationThe filtrate was concentrated
6. customto provide a black residue which
7. customwas purified by preparative HPLC
8. washeluting with TFA/ACN/H2O
9. customThe fractions were dried down in vacuo