Sodium cyanoborohydride → HCID 66611333, compound

Participants

Reaction Conditions

Reaction Steps

(S)-3-Methylmorpholine (Aldrich, 0.105 g, 1.041 mmol) and 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinaldehyde (Example 143, Step 2; 0.310 g, 0.520 mmol) were suspended in THF (3 mL) and titanium (IV) ethoxide (0.60 mL, 2.90 mmol) was added. The mixture was sealed and heated at 70° C. overnight. The light brown solution was cooled to 0° C. and excess sodium cyanoborohydride (0.327 g, 5.20 mmol) was added, and the mixture was stirred at 0° C. for 2 h. The resulting solution was quenched with a couple drop of MeOH followed by water. DCM was added to the entire mass and vigorously stirred for 10 min. The mixture was filtered and passed through a short path of Celite® (diatomaceous earth). The filter cake was washed with DCM (3×10 mL). The combined organic phases were concentrated to give a crude residue. Flash column chromatographic purification (short column, SiO2, 100% DCM to 5% MeOH in DCM) provided (S)-4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-((3-methylmorpholino)methyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (375 mg) as a yellow solid, which was deprotected under similar conditions according to the procedure reported previously (Example 178, Step 4) to afford the title compound (199 mg, 82%) as a yellow solid. m/z (ESI, +ve ion) 441 (M+H)+. 1H NMR (400 MHz, CDCl3) δ (rotatomer mixtures) 12.09 (br. s., 1H) 9.01 (br. s., 1H) 8.15-8.56 (m, 2H) 8.05 (br. s., 1H) 7.26 (br. s., 1H) 4.88-6.53 (m, 1H) 4.32 (br. s., 1H) 4.03 (br. s., 3H) 3.84 (br. s., 4H) 3.57 (br. s., 2H) 2.91 (br. s., 2H) 2.55 (br. s., 3H) 1.21 (d, J=5.28 Hz, 3H).

Provenance & Evidence