(6-Bromo-4-{4-[(dimethylamino)methyl]piperidin-1-yl}quinolin-3-yl)(cyclopropyl)methanone → [6-(3-Chloro-5-fluoro-4-hydroxyphenyl)-4-{4-[(dimethylamino)methyl]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]([CH3:26])[CH3:25])[CH2:19][CH2:18]1.[Cl:27][C:28]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[C:30]([F:43])[C:29]=1[OH:44]>>[Cl:27][C:28]1[CH:33]=[C:32]([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[CH2:18][CH2:19][CH:20]([CH2:23][N:24]([CH3:26])[CH3:25])[CH2:21][CH2:22]2)[CH:31]=[C:30]([F:43])[C:29]=1[OH:44]Participants
3
Reactant 2
Product 1
Procedure
Following general procedure D, (6-bromo-4-{4-[(dimethylamino)methyl]piperidin-1-yl}quinolin-3-yl)(cyclopropyl)methanone (30 mg, 0.072 mmol) was reacted with 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (41 mg, 0.150 mmol) to afford the desired product (22.3 mg, 64%) as a yellow solid: 1H NMR (500 MHz, CD3OD) δ 8.76 (s, 1H), 8.25 (d, J=1.6 Hz, 1H), 8.10-7.95 (m, 2H), 7.55-7.46 (m, 1H), 7.42 (dd, J=11.7, 2.3 Hz, 1H); 3.53 (d, J=12.7 Hz, 2H), 3.22 (t, J=11.6 Hz, 2H), 2.61 (d, J=6.6 Hz, 2H), 2.59-2.51 (m, 1H), 2.48 (s, 6H), 1.96 (d, J=10.0 Hz, 3H), 1.69-1.56 (m, 2H), 1.35-1.28 (m, 2H), 1.28-1.16 (m, 2H); ESI MS m/z 482 [C27H29ClFN3O2+H]+; HPLC 98.0% (AUC), tR=10.47 min.
Sources & evidence
- ORD record
- ord-2b9cbd4f83364178a4ce2c3557365705
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09120749B2
Reaction notes
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