Sodium Bicarbonate → 3'-Chloro-4-(1,3,5-trimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine

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Reaction Steps

To a suspension of 3′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (2.11 g, 7.77 mmol, 1 eq) in tetrahydrofuran (20 mL) add 1,3,5-trimethyl-1H-pyrazole-4-carbaldehyde (1.61 g, 11.65 mmol, 1.5 eq). Stir for 10 min and add sodium triacetoxyborohydride (4.20 g, 19.40 mmol, 2.5 eq) in one portion. Stir at room temperature under nitrogen for 1 hr., then add additional 1,3,5-trimethyl-1H-pyrazole-4-carbaldehyde (0.50 g, 3.6 mmol, 0.47 eq). Stir for 30 min., add saturated aq. sodium hydrogen carbonate (100 mL) slowly, and then extract with DCM (3×50 mL). Pass the combined DCM extracts through an IST Phase Separator Frit®, concentrate and purify (silica gel chromatography, eluting with 2:98 to 5:95 methanol:DCM), to give 3′-chloro-4-(1,3,5-trimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl as a white powder (2.468 g, 98%). MS (ES): m/z=321 [M+H]+.

Provenance & Evidence