Carbon Dioxide → HCID 56654139, compound

Participants

Reaction Steps

The titled compound was synthesized by procedures and steps analogous to those described in Example 5 above, but using 3-chloro-1-fluoro-7-(2-fluoropyridin-3-yl)spiro[chromeno[2,3-c]pyridine-5,3′-pyrrolo[3,4-c]pyridin]-1′-amine 2,2,2-trifluoroacetate (14d) and in step 4. 1-Fluoro-7-(2-fluoropyridin-3-yl)-3-(2-fluoropyridin-4-yl)spiro[chromeno[2,3-c]pyridine-5,3′-pyrrolo[3,4-c]pyridin]-1′-amine 2,2,2-trifluoroacetate (14e, 77 mg) was subjected to chromatography using supercritical CO2 (additives 26% MeOH with 20 mM NH3) on a Chrialcel ADH column (21×250 mm, 5 μm) eluting at a flow rate 65 ml/min (100 bar pressure, 40° C. column temperature). The first peak (retention time=5.3 min) provided (S)-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-7-(2-fluoropyridin-3-yl)spiro[chromeno[2,3-c]pyridine-5,1′-isoindol]-3′-amine (Example 14-A; >99% ee), and the second peak (retention time=7.0 min) provided (R)-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-7-(2-fluoropyridin-3-yl)spiro[chromeno[2,3-c]pyridine-5,1′-isoindol]-3′-amine (Example 14-B; TFA salt; >99% ee).

Provenance & Evidence