反应详情

TFA (2 mL) was added to a solution of 4-oxetan-3-ylpiperazine-1-carboxylic acid tert-butyl ester (150 mg, 0.62 mmol) in DCM (10 mL) and the mixture was stirred at ambient temperature for 30 min, then loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo to give 1-oxetan-3-ylpiperazine as a colourless oil. A solution of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (200 mg, 0.51 mmol), 1-oxetan-3-ylpiperazine (88 mg, 0.62 mmol) and molecular sieves (4 Å, powdered, 1 g) in DCE (10 mL) was stirred at ambient temperature for 5 h. Sodium triacetoxyborohydride (162 mg, 0.76 mmol) was added and the mixture stirred for 18 h, then loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; 100:0 to 99:1 to 98:2 to 95:5) to afford 513 as a white solid (98 mg, 37%). LCMS (Method I): RT=2.43 min, M+H+=518. 1H NMR (CDCl3, 400 MHz) δ 8.01 (dd, J=6.9, 2.4 Hz, 1 H); 7.78 (m, 1 H); 7.33-7.23 (m, 2 H); 4.70-4.60 (m, 4 H); 4.35 (m, 4 H); 3.97-3.75 (m, 7 H); 3.79 (s, 2 H); 3.57-3.49 (m, 1 H); 3.37 (q, J=7.5 Hz, 2 H); 2.66 (m, 4 H); 2.42 (m, 4 H); 1.46 (t, J=7.5 Hz, 3 H)

1. washThe cartridge was then washed with methanol
2. washthe desired product was subsequently eluted
3. customThe product was collected
4. concentrationconcentrated in vacuo
5. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; 100:0 to 99:1 to 98:2 to 95:5)