Lithium Hexamethyldisilazide → (R)-4-(2-(5-isopropyl-6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Steps

To a solution of (R)-4-(2-fluoro-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (Examples 145 and 146) 0.380 g, 0.598 mmol) and 5-isopropyl-6-methoxypyridin-3-amine (0.149 g, 0.897 mmol) in 3 mL THF at 0° C. was added lithium bis(trimethylsilyl)amide 1.0 M in THF (2.69 mL, 2.69 mmol) dropwise via syringe over 1 min. The dark red reaction was allowed to stir 30 min and was quenched by addition of saturated aq. NH4Cl. The reaction was partitioned between water and DCM. The aqueous layer was extracted with DCM 3 times, and the combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography (80 g column) using 20-100% EtOAc/hexane followed by 10% MeOH/EtOAc to elute the desired product. The product-containing fractions were concentrated to afford (R)-4-(2-(5-isopropyl-6-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.097 g, 0.124 mmol, 21% yield) as a red oil. m/z (ESI, +ve ion) 782 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 11.59 (s, 1H), 8.70 (d, J=2.2 Hz, 1H), 8.15-8.29 (m, 2H), 7.77 (d, J=2.5 Hz, 1H), 7.15-7.25 (m, 4H), 6.77-6.96 (m, 4H), 4.71-4.97 (m, 4H), 3.95 (s, 3H), 3.82 (s, 3H), 3.79 (s, 3H), 3.53 (q, J=6.8 Hz, 1H), 3.11-3.20 (m, 5H), 2.69 (s, 3H), 2.47-2.63 (m, 7H), 1.38 (d, J=6.7 Hz, 3H), 1.21 (d, J=6.8 Hz, 6H).

Provenance & Evidence