4-((Pyrimidin-2-ylamino)methyl)benzaldehyde synthesis

Yield:-

Reaction Conditions:

with manganese(IV) oxide in dichloromethane;N,N-dimethyl-formamide at 20; for 19 h;

Steps:

16

To a solution of (4-((pyrimidin-2-ylamino)methyl)phenyl)methanol (prepared using the method of WO-2006-074428, herein incorporated by reference in its entirety) (4.4 g, 20.6 mmol) in a 3:1 mixture of CH₂C1₂/DMF (100 mL) at room temperature was added manganese dioxide (10.7 g, 123.6 mmol). After stirring the reaction for 19 hours at room temperature, the mixture was filtered through celite and concentrated in vacuo to remove CH₂Cl₂. The residue was diluted with aqueous saturated NaHCO₃ and extracted with EtOAc. The organic layer was dried (MgSO₄), filtered and concentrated in vacuo. The crude residue was purified over silica (2% MeOH /CHCl₃ to 5% MeOH /CHCl₃) to afford 3.34 g of 16: ¹H NMR (400 MHz, J₆-DMSO) δ 9.91 (s, IH), 8.22 (d, J= 4.4 Hz, 2H), 7.80 (d, J= 8.4 Hz, 3H), 7.46 (d, J= 8.0 Hz, 2H), 6.55 (t, J= 4.8 Hz, IH), 4.54 (d, J= 6.0 Hz, 2H).

References:

WO2008/112156,2008,A1 Location in patent:Page/Page column 571-572