Sodium triacetoxyborohydride → 2-[4-(5-Chloro-7-morpholin-4-yl-thiazolo[4,5-d]pyrimidin-2-ylmethyl)piperazin-1-yl]isobutyramide

Participants

Reaction Steps

A mixture of 5-chloro-7-morpholin-4-yl-thiazolo[4,5-d]pyrimidine-2-carbaldehyde (250 mg, 0.88 mmol), 2-piperazin-1-yl-isobutyramide (173 mg, 1.01 mmol) and 4 Å molecular sieves (1.0 g) in 1,2-dichloroethane (15 mL) was stirred at RT under nitrogen atmosphere for 4 h. Sodium triacetoxyborohydride (280 mg, 1.32 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 on an Isolute® SCX-2 cartridge (25 g). The cartridge was washed with DCM/MeOH and the desired product was subsequently eluted using a mixture of 2 M NH3 in MeOH and DCM. The resulting residue was further purified by column chromatography (Si—PCC, MeOH:DCM: gradient 0:100 to 6:94). The solvents were reduced in vacuo to afford the title compound as a yellow solid (275 mg, 60%). LCMS (Method H): RT 2.41 min, [M+H]+ 440. 1H NMR (400 MHz, CDCl3): δ 7.04 (1 H, br s), 5.22 (1 H, br s), 3.97-3.95 (6 H, m), 3.85 (4 H, t, J=4.80 Hz), 2.67 (8 H, m), 1.25 (6 H, s)

Provenance & Evidence