L-Alaninol → 3-(Tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-(4-chloro-3-fluoro-phenyl)-(1-methyl-1H-pyrazol-4-yl)-methyl]-amide
Reaction equation
N[C@@H:2]([CH3:5])[CH2:3][OH:4].[NH2:6][CH:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.Cl.FC1C=[C:17]([C@@H:23]([C:25]2C=N[N:28]([CH3:30])[CH:29]=2)N)[CH:18]=[CH:19]C=1OC.Cl.[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([C@@H:39]([C:41]2[CH:42]=[N:43][N:44]([CH3:46])[CH:45]=2)[NH2:40])=[CH:35][C:34]=1[F:47]>>[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([C@H:39]([NH:40][C:3]([C:2]2[CH:5]=[C:23]3[C:17](=[CH:18][CH:19]=2)[CH:30]=[N:28][C:29]([NH:6][CH:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)=[CH:25]3)=[O:4])[C:41]2[CH:42]=[N:43][N:44]([CH3:46])[CH:45]=2)=[CH:35][C:34]=1[F:47]Participants
Reactant 4
Product 1
Procedure
3-(Tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-(4-chloro-3-fluoro-phenyl)-(1-methyl-1H-pyrazol-4-yl)-methyl]-amide (II-11) was prepared analogously except in step 2, (S)-2-aminopropan-1-ol was replaced with 4-amino-tetrahydropyran and in step 5, 50c was replaced with (S)-(4-chloro-3-fluorophenyl)(1-methyl-1H-pyrazol-4-yl)methanamine hydrochloride (50a). 1H NMR (400 MHz, DMSO-d6) δ 9.26 (d, J=8.4 Hz, 1H), 8.91 (s, 1H), 8.10 (s, 1H), 7.84 (d, J=8.6 Hz, 1H), 7.57 (t, J=8.4 Hz, 1H), 7.57 (s, 1H), 7.53 (dd, J=8.5, 1.4 Hz, 1H), 7.48 (dd, J=10.6, 1.9 Hz, 1H), 7.37 (s, 1H), 7.32 (dd, J=8.4, 1.8 Hz, 1H), 6.73 (s, 1H), 6.52 (d, J=7.9 Hz, 1H), 6.32 (d, J=8.3 Hz, 1H), 3.93-3.86 (m, 2H), 3.86-3.80 (m, 1H), 3.79 (s, 3H), 3.44 (td, J=11.5, 2.0 Hz, 2H), 1.92 (d, J=10.4 Hz, 2H), 1.49 (ddd, J=15.4, 12.0, 4.3 Hz, 2H).
Sources & evidence
- ORD record
- ord-a0a26847e2c7441586dc50fa952badc9
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09388171B2
Reaction notes
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