Hydrochloric Acid → HCID 58949460, compound

Participants

Reaction Steps

A round-bottomed flask was charged with 2-(3-fluoro-4-(2-(piperidin-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenylamino)-N-(4-fluorophenyl)nicotinamide (Example 177, Step D, 47 mg, 0.084 mmol), formaldehyde (7.7 mg, 0.084 mmol) 33% in water and THF (5 mL). The mixture was stirred for 30 minutes and then NaBH(OAc)3 (18 mg, 0.084 mmol) was added. The mixture was stirred for another 30 minutes and then HCl (1N, 1 mL) was added. The acid was neutralized with Na2CO3 and the mixture extracted with EtOAc. The organics were dried over sodium sulfate, filtered and concentrated to get product as a free base. The crude product was diluted in MeOH (2 mL) and HCl (0.1 mL, 4N Dioxane) added. The mixture was concentrated under high vacuum to get product (34 mg, 67%) as a yellow solid. LRMS (esi+) 572 m/z (M+1) detected. 1H NMR (CDCl3, 400 MHz) δ 10.65 (s, 1H), 10.55 (br s, 2H). 9.14 (s, 1H), 8.39 (d, J=6 Hz, 2H), 8.34 (m, 1H), 8.18 (d, J=8 Hz, 1H), 8.03 (d, J=13 Hz, 1H), 7.65 (m, 2H), 7.12 (m, 4H), 6.78 (m, 1H), 6.50 (d, J=5.5 Hz, 1H), 3.36 (m, 2H), 3.13 (m, 1H), 2.81 (m, 2H), 2.26 (m, 4H), 2.05 (s, 3H).

Provenance & Evidence