L-Alaninol → 3-(Tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-(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.[F:14][C:15]1[CH:16]=[C:17]([C@@H:23]([C:25]2[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=2)[NH2:24])[CH:18]=[CH:19][C:20]=1OC.Cl.FC1C=[C:35]([C@@H:39]([C:41]2C=N[N:44]([CH3:46])[CH:45]=2)N)[CH:36]=[CH:37]C=1>>[F:14][C:15]1[CH:16]=[C:17]([C@H:23]([NH:24][C:3]([C:2]2[CH:5]=[C:39]3[C:35](=[CH:36][CH:37]=2)[CH:46]=[N:44][C:45]([NH:6][CH:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)=[CH:41]3)=[O:4])[C:25]2[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=2)[CH:18]=[CH:19][CH:20]=1Participants
Reactant 4
Product 1
Procedure
3-(Tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-(3-fluoro-phenyl)-(1-methyl-1H-pyrazol-4-yl)-methyl]-amide (II-9) 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)-(3-fluoro-phenyl)(1-methyl-1H-pyrazol-4-yl)methanamine hydrochloride (50h). 1H NMR (400 MHz, DMSO) δ 9.26 (d, J=8.5 Hz, 1H), 8.91 (s, 1H), 8.10 (s, 1H), 7.84 (d, J=8.6 Hz, 1H), 7.57 (s, 1H), 7.54 (dd, J=8.5, 1.4 Hz, 1H), 7.40 (td, J=8.0, 6.1 Hz, 1H), 7.36 (s, 1H), 7.30-7.24 (m, 2H), 7.09 (td, J=8.6, 2.5 Hz, 1H), 6.73 (s, 1H), 6.51 (d, J=8.0 Hz, 1H), 6.33 (d, J=8.5 Hz, 1H), 3.92-3.86 (m, 2H), 3.86-3.80 (m, 1H), 3.79 (s, 3H), 3.44 (td, J=11.8, 2.0 Hz, 2H), 1.92 (d, J=10.5 Hz, 2H), 1.49 (ddd, J=15.6, 12.0, 4.2 Hz, 2H).
Sources & evidence
- ORD record
- ord-445d0ab67b794b37ae6d13226b20a8a9
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09388171B2
Reaction notes
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