2-Chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol → (S)-(4-(6-(3-aminopiperidin-1-yl)pyridin-3-ylamino)-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-3-yl)(cyclopropyl)methanone

Participants

Reaction Steps

Following general procedure D, (S)-tert-butyl 1-(5-(6-bromo-3-(cyclopropanecarbonyl)quinolin-4-ylamino)pyridin-2-yl)piperidin-3-ylcarbamate (100 mg, 0.17 mmol) was reacted with 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (71 mg, 0.26 mmol) to obtain the protected intermediate which was subjected to general procedure A-2 to afford the desired product (27 mg, 30% over 2 steps) as an orange-yellow solid: 1H NMR (500 MHz, MeOD TFA-d) δ 9.40 (br s, 1H), 8.28-8.15 (m, 2H), 8.06 (br s, 1H), 8.00 (d, J=8.8 Hz, 1H), 7.66 (dd, J=9.1, 2.8 Hz, 1H), 7.16-7.05 (m, 3H), 4.53 (d, J=11.0 Hz, 1H), 4.01 (dd, J=13.4, 4.6 Hz, 1H), 3.41-3.23 (m, 3H), 2.86 (br s, 1H), 2.23-2.15 (m, 1H), 1.99-1.88 (m, 1H), 1.79-1.66 (m, 2H), 1.27-1.16 (m, 4H). ESI MS m/z 532 [C29H27ClFN5O2+H]+; HPLC>99.0% (AUC), tR=10.78 min.

Provenance & Evidence