Lithium Hexamethyldisilazide → Tert-butyl 5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-ylamino)pyridin-2-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

LiHMDS (Aldrich) (2.44 mL, 2.44 mmol) was added dropwise at 0° C. to a stirred solution of 4-(2-fluoro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.507 g, 0.815 mmol) and tert-butyl 5-aminopyridin-2-ylcarbamate (0.204 g, 0.976 mmol) in THF (2 mL). The dark red mixture was stirred at 0° C. for 2 h. More LiHMDS (1.6 mL, 1.6 mmol) was added dropwise at 0° C. and stirring was continued for another 30 min. The reaction was quenched by adding 0.3 mL of sat'd NH4Cl. The reaction mixture was partitioned between water (40 mL) and EtOAc (40 mL). The aqueous phase was extracted with EtOAc (2×30 mL). The combined organic layers were washed with saturated aqueous sodium chloride (40 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (100 g, eluent: iPrOH (w/10% NH4OH) in CHCl3 0%-10%) to give tert-butyl 5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-ylamino)pyridin-2-ylcarbamate (0.306 g, 46% yield). 1H NMR (400 MHz, CDCl3) δ 11.76 (s, 1H); 8.71 (d, J=2.54 Hz, 1H); 8.42 (d, J=2.35 Hz, 1H); 8.23 (d, J=2.35 Hz, 1H); 7.94 (dd, J=9.00, 2.54 Hz, 1H); 7.83 (d, J=9.00 Hz, 1H); 7.15-7.25 (m, 5H); 6.86 (dd, J=11.15, 8.61 Hz, 4H); 4.83 (d, J=10.17 Hz, 4H); 3.76-3.85 (m, 6H); 3.50 (s, 2H); 3.18 (br s., 4H); 2.71 (s, 3H); 2.59 (s, 3H); 2.55 (t, J=4.50 Hz, 4H); 1.53 (s, 9H).

Provenance & Evidence