L-Alaninol → N-((S)-1-(3-Chloro-4-fluorophenyl)-2-hydroxyethyl)-3-(tetrahydrofuran-3-ylamino)isoquinoline-6-carboxamide
Reaction equation
N[C@@H:2]([CH3:5])[CH2:3][OH:4].[NH2:6][CH:7]1[CH2:11][CH2:10][O:9][CH2:8]1.Cl.FC1C=[C:16]([C@@H:22]([C:24]2C=N[N:27]([CH3:29])[CH:28]=2)N)[CH:17]=[CH:18]C=1OC.Cl.[NH2:31][C@@H:32]([C:35]1[CH:40]=[CH:39][C:38]([F:41])=[C:37]([Cl:42])[CH:36]=1)[CH2:33][OH:34]>>[Cl:42][C:37]1[CH:36]=[C:35]([C@H:32]([NH:31][C:3]([C:2]2[CH:5]=[C:22]3[C:16](=[CH:17][CH:18]=2)[CH:29]=[N:27][C:28]([NH:6][CH:7]2[CH2:11][CH2:10][O:9][CH2:8]2)=[CH:24]3)=[O:4])[CH2:33][OH:34])[CH:40]=[CH:39][C:38]=1[F:41]Participants
5
Reactant 4
Product 1
Procedure
N—((S)-1-(3-Chloro-4-fluorophenyl)-2-hydroxyethyl)-3-(tetrahydrofuran-3-ylamino)isoquinoline-6-carboxamide (II-38) was prepared analogously except in step 2, (S)-2-aminopropan-1-ol was replaced with 3-amino-tetrahydrofuran and in step 5, 50c was replaced with (S)-2-amino-2-(3-chloro-4-fluoro-phenyl)ethanol hydrochloride 62f. 1H NMR (500 MHz, DMSO-d6) δ 8.93 (s, 1H), 8.87 (d, J=8.5 Hz, 1H), 8.12 (s, 1H), 7.87 (d, J=8.5 Hz, 1H), 7.64 (dd, J=7.0, 2.0 Hz, 1H), 7.55 (d, J=8.5 Hz, 1H), 7.44-7.36 (m, 2H), 6.84 (d, J=6.5 Hz, 1H), 6.71 (s, 1H), 5.10-5.03 (m, 2H), 4.31 (m, 1H), 3.95 (m, 1H), 3.86 (m, 1H), 3.77-3.75 (m, 2H), 3.73 (m, 1H), 3.61 (m, 1H), 2.23 (m, 1H), 1.87 (m, 1H).
Sources & evidence
- ORD record
- ord-5b3ba0a30b7d482caef7b6cb88431a30
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09388171B2
Reaction notes
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