Tetrahydrofuran → (S)-methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

Participants

Reaction Conditions

Reaction Steps

To a stirred yellow solution of methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (1 g, 2.61 mmol) in anhydrous toluene (25 mL) was added 1.1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (0.947 mL, 1.042 mmol). The mixture was cooled to −35° C. and a solution of 1M catechoborane/THF (3.65 mL, 3.65 mmol) was added over 10 min. After 30 min, the reaction mixture was slowly warmed to −15 C and stirred for additional 30 min. and diluted with EtOAc (30 mL) and sat. Na2CO3 (10 mL). The mixture was stirred vigorously for 30 min, and the organic phase washed with sat Na2CO3 (2×5 mL), dried (Na2SO4), filtered, concentrated and the residue was purified by silica gel chromatography (5-70% EtOAc/hexane) to afford desired (S)-methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (888 mg, 2.301 mmol, 88% yield) as off-white solid. EE=95.4% 1H NMR (500 MHz, CDCl3) δ 7.77-7.71 (m, 2H), 7.19 (d, J=7.6 Hz, 1H), 6.93 (s, 1H), 5.78 (d, J=2.7 Hz, 1H), 3.86 (s, 3H), 3.56 (d, J=2.7 Hz, 1H), 2.89-1.81 (m, 4H), 2.64 (s, 3H), 1.86 (dt, J=6.5, 3.3 Hz, 4H). LCMS (M+H)=386.3.

Provenance & Evidence