{6-Bromo-4-[4-(pyrrolidin-1-ylmethyl)piperidin-1-yl]quinolin-3-yl}(cyclopropyl)methanone → {6-(3-Chloro-5-fluoro-4-hydroxyphenyl)-4-[4-(pyrrolidin-1-ylmethyl)piperidin-1-yl]quinolin-3-yl}(cyclopropyl)methanone
Reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])=[C:5]2[N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][N:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)[CH2:19][CH2:18]1.[Cl:29][C:30]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[C:32]([F:45])[C:31]=1[OH:46]>>[Cl:29][C:30]1[CH:35]=[C:34]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][C:6]([C:12]([CH:14]2[CH2:16][CH2:15]2)=[O:13])=[C:5]3[N:17]2[CH2:22][CH2:21][CH:20]([CH2:23][N:24]3[CH2:25][CH2:26][CH2:27][CH2:28]3)[CH2:19][CH2:18]2)[CH:33]=[C:32]([F:45])[C:31]=1[OH:46]Participants
3
Reactant 2
Product 1
Procedure
Following general procedure D, {6-bromo-4-[4-(pyrrolidin-1-ylmethyl)piperidin-1-yl]quinolin-3-yl}(cyclopropyl)methanone (30 mg, 0.068 mmol) was reacted with 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (27 mg, 0.099 mmol) to afford the desired product (24.3 mg, 71%) as a yellow solid: 1H NMR (500 MHz, CD3OD) δ 8.79 (s, 1H), 8.24 (d, J=1.7 Hz, 1H), 8.06-7.96 (m, 2H), 7.53-7.49 (m, 1H), 7.42 (dd, J=11.7, 2.2 Hz, 1H), 3.53 (d, J=12.8 Hz, 2H), 3.28-3.15 (m, 6H), 3.09 (d, J=7.0 Hz, 2H), 2.62-2.54 (m, 1H), 2.14-2.02 (m, 5H), 1.99 (d, J=12.5 Hz, 2H), 1.77-1.63 (m, 2H), 1.36-1.28 (m, 2H), 1.28-1.17 (m, 2H); ESI MS m/z 508 [C29H31ClFN3O2+H]+; HPLC 98.1% (AUC), tR=10.69 min.
Sources & evidence
- ORD record
- ord-dcaef34120814b40bdff52d278b8e12a
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09120749B2
Reaction notes
Loading…