2-Chloro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol → (R)-(4-(6-(3-aminopiperidin-1-yl)pyridin-3-ylamino)-6-(3-chloro-4-hydroxy-5-methoxyphenyl)quinolin-3-yl)(cyclopropyl)methanone

Participants

Reaction Steps

Following general procedure D, (R)-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-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (74 mg, 0.26 mmol) to obtain the protected intermediate which was subjected to general procedure A-2 to afford the desired product (30 mg, 32% over 2 steps) as an orange-yellow solid: 1H NMR (500 MHz, MeOD+TFA-d) δ 9.40 (br s, 1H), 8.28-8.20 (m, 2H), 8.10 (br s, 1H), 8.00 (d, J=8.8 Hz, 1H), 7.65 (dd, J=9.1, 2.8 Hz, 1H), 7.05 (d, J=9.1 Hz, 1H), 6.99 (s, 1H), 6.83 (br s, 1H), 4.55-4.49 (d, J=11.6 Hz, 1H), 4.04-3.95 (m, 1H), 3.91 (s, 3H), 3.28-3.18 (m, 3H), 2.87 (br s, 1H), 2.22-2.14 (m, 1H), 1.96-1.87 (m, 1H), 1.76-1.62 (m, 2H), 1.28-1.16 (m, 414).; ESI MS m/z 544 [C30H30ClN5O3+H]+; HPLC>99.0% (AUC), tR=10.74 min.

Provenance & Evidence