Methanol → HCID 86633436, compound

Participants

Reaction Steps

To a solution of 6,7-dichloro-4-{4-fluoro-3-[(4-oxopiperidin-1-yl)carbonyl]benzyl}pyrrolo[1,2-a]pyrazin-1(2H)-one (Example 232, which was prepared as described in Example 13) (1 eq) in THF (0.6 M) were added titanium(IV) isopropoxide (1.6 eq), 3,3-difluoroazetidine hydrochloride (1.6 eq) and DIPEA (1.6 eq). The reaction mixture was stirred for 30 minutes at RT and then a solution of NaBH3(CN) (1.3 eq) in MeOH (0.16 M) was added. After 30 minutes water was added, and the resulting precipitate was filtered and washed with MeOH. The filtrate was evaporated and purified by RP-HPLC (column Symmetry RP 18, 7 μm, 19×300 mm, gradient A: H2O+0.1% TFA; B: MeCN+0.1% TFA) and the pooled fractions were evaporated under reduced pressure to yield the title compound. 1H NMR (300 MHz, DMSO-d6+TFA, 300K) δ 10.94-10.88 (1H, m), 7.38-7.10 (4H, m), 6.64-6.55 (1H, m), 4.91-4.78 (4H, m), 4.62-4.50 (1H, m), 4.44-4.25 (2H, m), 3.61-3.32 (2H, m), 3.10-2.90 (1H, m), 2.82-2.66 (1H, m), 2.10-1.72 (2H, m), 1.48-1.0 (2H, m). MS (ES+) C23H21Cl2F3N4O2 requires: 512/514, found: 513/515 (M+H)+.

Provenance & Evidence