L-Alaninol → 3-(Tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(3-fluoro-4-methoxy-phenyl)-2-hydroxy-ethyl]-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.[NH2:32][C@@H:33]([C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[C:38]([F:44])[CH:37]=1)[CH2:34][OH:35]>>[F:44][C:38]1[CH:37]=[C:36]([C@H:33]([NH:32][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])[CH2:34][OH:35])[CH:41]=[CH:40][C:39]=1[O:42][CH3:43]Participants
5
Reactant 4
Product 1
Procedure
3-(Tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(3-fluoro-4-methoxy-phenyl)-2-hydroxy-ethyl]-amide (II-17) 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)-2-amino-2-(3-fluoro-4-methoxyphenyl)ethanol hydrochloride (62d). 1H NMR (500 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.76 (d, J=8.5 Hz, 1H), 8.08 (s, 1H), 7.85 (d, J=8.5 Hz, 1H), 7.53 (d, J=9.0 Hz, 1H), 7.27 (d, J=13.0 Hz, 1H), 7.17 (d, J=8.5 Hz, 1H), 7.11 (t, J=8.5 Hz, 1H), 6.73 (s, 1H), 6.55 (d, J=8.0 Hz, 1H), 5.06-5.02 (m, 1H), 4.96 (t, J=5.5 Hz, 1H), 3.91-3.89 (m, 2H), 3.81 (s, 3H), 3.70-3.61 (m, 2H), 3.46-3.42 (m, 3H), 1.94-1.91 (m, 2H), 1.52-1.45 (m, 2H).
Sources & evidence
- ORD record
- ord-8d64b0ecc86e45fbabc45d9f3428ac68
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09388171B2
Reaction notes
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