Acetic Acid → 2-(1-((5-(2-methyl-1H-benzo[d]imidazol-1-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-3-yl)propan-2-ol

Participants

Reaction Steps

A mixture of 5-(2-methylbenzoimidazol-1-yl)-7-morpholin-4-yl-thiazolo[5,4-d]pyrimidine-2-carbaldehyde (78 mg, 0.2 mmol), 2-piperidin-3-yl-propan-2-ol (43 mg, 0.3 mmol) trimethyl orthoformate (0.109 mL, 1.0 mmol) and glacial acetic acid (0.017 mL, 0.3 mmol) in 1,2-dichloroethane (2 mL) was stirred at RT under nitrogen atmosphere for 1 h. Sodium triacetoxyborohydride (85 mg, 0 4 mmol) was added and the resulting reaction mixture was stirred at RT for 16 h. The solvent was reduced in vacuo and the residue was loaded onto an Isolute® SCX-2 cartridge (10g). The cartridge was washed with DCM/MeOH, the desired product was subsequently eluted using a mixture of 2M NH3 in MeOH and DCM. The residue was purified by column chromatography (Si—PCC, acetone:cyclohexane: 10:90 to 35:65 by volume). Solvents were reduced in vacuo to afford the title compound as a white solid. The resulting solid was further purified by reverse phase HPLC (MeOH:H2O+0.1% HCCOH, gradient 10:90 to 90:10 over 25 min). The solvent was reduced in vacuo and the aqueous residue freeze dryed to afford 362 as a white solid (23 mg, 23%). LCMS (Method G): RT 6.73 min, [M+H]+ 508. 1H NMR (400 MHz, CDCl3): δ 8.18 (1H, s), 8.04-8.03 (1 H, m), 7.70-7.69 (1 H, m), 7.27-7.26 (2 H, m), 4.38 (4 H, br s), 3.90 (2 H, s), 3.85 (4 H, t, J=4.74 Hz), 3.18 (2 H, m), 2.91 (5 H, m), 2.28-2.15 (2 H, m), 1.81 (2 H, m), 1.75-1.60 (2 H, m), 1.20 (3 H, s), 1.15 (3 H, s)

Provenance & Evidence