Nitrogen → 5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde

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Reaction Steps

A stock solution of 4-(5-(1,3-dioxolan-2-yl)-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (Example 143, Step 1) (5.85 g, 11.30 mmol) in benzene (50 mL) contained in a 250 mL round-bottomed flask with stir bar was frozen and lyophilized overnight (pale yellow solid obtained). The flask was opened to N2 and THF (50 mL) was added followed by 6-methoxypyridin-3-amine (1.332 mL, 12.43 mmol). The solution was cooled in an ice bath and LiHMDS (44 mL of a 1.0 M solution in THF, 44 mmol) was added. The mixture was stirred for 40 min and then quenched with water (3 mL) and concentrated to dryness. The residue was taken up in a mixture of DCM and 2 N aqueous HCl and stirred for 30 min. The product was extracted into DCM from 2 N HCl, washed with saturated aqueous NaHCO3, dried (MgSO4) and concentrated to give a brown solid. This was dissolved in DCM and purified by flash chrormatography (30% EtOAc, 10% DCM, 60% hexane) to give 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde (3.98 g, 6.89 mmol, 61.0% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 12.09 (s, 1H); 9.90 (s, 1H); 9.14 (d, J=2.35 Hz, 1H); 8.77 (d, J=2.35 Hz, 1H); 8.31 (d, J=2.74 Hz, 1H); 7.87 (dd, J=8.80, 2.74 Hz, 1H); 7.28 (d, J=8.61 Hz, 2H); 7.21 (d, J=8.80 Hz, 2H); 6.87-6.94 (m, 2H); 6.78-6.87 (m, 3H); 4.83 (d, J=7.24 Hz, 4H); 3.85 (s, 3H); 3.74 (s, 3H); 3.69 (s, 3H); 2.58 (s, 3H). m/z (ESI, +ve ion) 578 (M+H)+.

Provenance & Evidence