(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acid → 4-fluoro-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide
Reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15](CC3C=CC(OC)=CC=3)[C:16]3[CH:21]=[CH:20][N:19]=[CH:18][N:17]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[C:5]([F:31])=[CH:4][N:3]=1.[CH3:32][O:33][C:34]1[CH:39]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:37]=[CH:36][C:35]=1B(O)O>>[F:31][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[C:8]([S:12]([NH:15][C:16]3[CH:21]=[CH:20][N:19]=[CH:18][N:17]=3)(=[O:14])=[O:13])[CH:7]=2)[C:2]([C:35]2[CH:36]=[CH:37][C:38]([C:40]([F:43])([F:42])[F:41])=[CH:39][C:34]=2[O:33][CH3:32])=[N:3][CH:4]=1Participants
3
Procedure
Example 216 was synthesized in a similar manner to Example 212, except that 1-chloro-4-fluoro-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (Intermediate QQQ) and (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid were used as the coupling partners. The final compound was purified via column chromatography (12 g silica gel column, gradient elution 25 to 100% EtOAc:Heptane) to afford 4-fluoro-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=8.74 (s, 1H), 8.59 (d, J=17.3 Hz, 2H), 8.35-8.13 (m, 1H), 8.06 (d, J=8.9 Hz, 1H), 7.77 (d, J=9.1 Hz, 1H), 7.62-7.56 (m, 1H), 7.54-7.46 (m, 2H), 3.75 (s, 3H). m/z (ESI) 479.2 (M+H)+.
Workup
- customThe final compound was purified via column chromatography (12 g silica gel column, gradient elution 25 to 100% EtOAc:Heptane)
Sources & evidence
- ORD record
- ord-797d69193ac1476d9c100b107f29d3c8
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09012443B2
Reaction notes
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