Sodium triacetoxyborohydride → 4-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-8-((3-(1,1-dioxo-thiomorpholino)azetidin-1-yl)methyl)-9H-purin-6-yl)morpholine

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Reaction Steps

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (1.2 g, 3.07 mmol), 4-azetidin-3-ylthiomorpholine-1,1-dioxide (640 mg, 3.37 mmol) and 4 Å powdered molecular sieves (2.5 g) in DCE (65 mL) was stirred at room temperature for 6.5 h before the addition of sodium triacetoxyborohydride (1.3 g, 6.13 mmol). The reaction mixture was stirred for 18 h then filtered through celite, washing with DCM. The organic phase was washed with brine (x 1) and concentrated in vacuo. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%). A mixture of the resulting yellow powder and 3-mercaptopropyl ethyl sulphide silica (250 mg) was stirred in a mixture of EtOH and DCM at 50° C. for 3 h. The mixture was filtered and concentrated in vacuo. The resulting oil was loaded onto an Isolute® SCX-2 cartridge which was washed with EtOH and the product eluted with 2M NH3/EtOH. The resulting oil was triturated with Et2O and dried in vacuo at 60° C. affording 354 as a pale yellow solid (1.26 g, 73%). LCMS (Method I): RT 2.43 min [M+H]+ 566.3. 1H NMR (CDCl3, 400 MHz): δ 8.02-7.97 (m, 1 H); 7.77-7.73 (m, 1 H); 7.29-7.22 (m, 2 H); 4.34 (m, 4 H); 3.89-3.80 (m, 9 H); 3.59 (m, 2 H); 3.39-3.23 (m, 3 H); 3.12-3.04 (m, 6 H); 2.85 (m, 4 H) and 1.44 (t, J=7.5 Hz, 3 H)

Provenance & Evidence