Trifluoroacetic acid methylene chloride → Hydrochloric Acid

Participants

Reaction Steps

In a similar manner as described in Example 110, (R)-tert-butyl 4-(4-(3-carbamoyl-6-(3-(4-methoxybenzamido)piperidin-1-yl)pyrazin-2-ylamino)-3-fluorophenyl)piperidine-1-carboxylate (200) was prepared using tert-butyl 4-(4-amino-3-fluorophenyl)piperidine-1-carboxylate. It was treated with 1:1 TFA/DCM at RT for 30 min, and (R)-3-(2-fluoro-4-(piperidin-4-yl)phenylamino)-5-(3-(4-methoxybenzamido)piperidin-1-yl)pyrazine-2-carboxamide (201) was isolated as HCl salt using reverse phase prep HPLC using 5 mM HCl (aq) and neat MeCN as mobile phases. MS found for C29H34FN7O3 as (M+H)+ 548.2, (M−H)− 546.3. UV: λ=257, 280, 306, 334, 369 nm. Proton NMR (CD3OD): δ 8.34 (1H, m), 7.79 (2H, d, J=9.0 Hz), 7.72 (1H, s), 7.03 (1H, d, J=12.5 Hz), 6.99 (2H, d, J=8.5 Hz), 6.96 (1H, d, J=9.5 Hz), 4.46 (1H, m), 4.18 (1H, m), 4.12 (1H, m), 3.86 (3H, m), 3.45 (1H, s), 3.42 (1H, s), 3.25 (2H, m), 3.08 (2H, m), 2.80 (1H, m), 2.11 (1H, m), 2.01-1.94 (3H, m), 1.81-1.70 (4H, m) ppm.

Provenance & Evidence