Benzenemethanamine, N-methyl-3-(2-pyrimidinyloxy)- synthesis

Yield:-

Reaction Conditions:

Stage #1: 3-(2-pyrimidinyl-oxy)benzaldehyde;methylaminewith sodium cyanoborohydride in tetrahydrofuran at 20; for 7 h;
Stage #2: with hydrogenchloride in tetrahydrofuran;dichloromethane;water;
Stage #3: in water; pH=10;

Steps:

F.3.2 Step 2:

To a solution of the aryl ether (1) from Step 1 (1.00 g, 5.00 mmol) and MeNH2 (3.00 mL, 2. 0 M in THF, 5.99 mmol) in MeOH (75 mL) at RT was added NaCNBH3 (377 mg, 5.99 MMOL). The reaction was stirred for 7 h before it was concentrated under reduced pressure. The residue was taken-up in a mixture of 1 N aq. HCL (20 mL) and CH2CL2 (5 mL). The aq. layer was separated, adjusted to pH 10, and extracted with CH2CI2-THE CH2CI2 EXTRACT WAS WASHED with brine, dried over GUS04 and concentrated. The residue was purified by column chromatography (silica gel, 10% MEOH in CH2Cl2) to furnish 363 mg of the benzylamine (2) as a faintly-colored oil.

References:

WO2005/5395,2005,A2 Location in patent:Page 73