Tetrahydro-4H-pyran-4-one → (S)-4-(2-chloro-9-methyl-6-(3-methylmorpholino)-9H-purin-8-yl)tetrahydro-2H-pyran-4-ol

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Reaction Conditions

Reaction Steps

To (S)-4-(2-chloro-9-methyl-9H-purin-6-yl)-3-methylmorpholine (100.0 mg, 0.374 mmol) in anhydrous THF (4.0 mL) at −78° C. under N2 was added freshly prepared lithium diisopropylamide in THF (2.0 eq.), and the reaction mixture was stirred at −78° C. After stirring for 2 h tetrahydro-4H-pyran-4-one (68.6 μL, 0.75 mmol, 2.0 eq.) was added. The reaction was then stirred at RT for 16 h and quenched with saturated aqueous sodium ammonium chloride solution. Volatile solvent was evaporated in vacuo, and the crude was diluted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate, water and brine, then dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 5 to 100% ethyl acetate in hexane). Crystallization from ether-hexane afforded the product (b-1) as a solid (111.3 mg, 81.0%). 1H NMR (CDCl3, 400 MHz). δ ppm 5.3 (broad s, 1H), 4.98 (broad s, 1H), 4.00 (dd, J=3.4 Hz, 1H), 3.97 to 3.79 (m, 7H), 3.79 to 3.71 (m, 2H), 3.60 (td, J=11.6, 2.7 Hz, 1H), 3.45 (broad s, 1H), 2.39 (m, 2H), 1.86 (d, J=13.2 Hz, 2H), 1.38 (d, J=6.8 Hz, 3H); LC-MS m/z (method A)=368/370 [M+H]+, RT=1.93 min.

Provenance & Evidence