L-Alaninol → 3-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-2-hydroxy-1-(4-methoxy-phenyl)-ethyl]-amide
Reaction equation
N[C@@H:2]([CH3:5])[CH2:3][OH:4].[F:6][C@H:7]1[C@@H:12]([NH2:13])[CH2:11][CH2:10][O:9][CH2:8]1.Cl.FC1C=[C:18]([C@@H:24]([C:26]2C=N[N:29]([CH3:31])[CH:30]=2)N)[CH:19]=[CH:20]C=1OC.Cl.[NH2:33][C@@H:34]([C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=1)[CH2:35][OH:36]>>[OH:36][CH2:35][C@@H:34]([NH:33][C:3]([C:2]1[CH:5]=[C:24]2[C:18](=[CH:19][CH:20]=1)[CH:31]=[N:29][C:30]([NH:13][C@H:12]1[CH2:11][CH2:10][O:9][CH2:8][C@H:7]1[F:6])=[CH:26]2)=[O:4])[C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=1Participants
Reactant 4
Product 1
Procedure
3-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-2-hydroxy-1-(4-methoxy-phenyl)-ethyl]-amide (II-43) was prepared analogously except in step 2, (S)-2-aminopropan-1-ol was replaced with (3S,4S)-3-fluorotetrahydro-2H-pyran-4-amine (71c) and in step 5, 50c was replaced with (S)-2-amino-2-(4-methoxyphenyl)ethanol hydrochloride (62c). 1H NMR (500 MHz, DMSO-d6): δ 8.93 (s, 1H), 8.80 (d, J=8.5 Hz, 1H), 8.09 (s, 1H), 7.87 (d, J=9.0 Hz, 1H), 7.56 (d, J=9.0 Hz, 1H), 7.33 (d, J=8.5 Hz, 2H), 6.90 (s, 1H), 6.89 (d, J=8.5 Hz, 2H), 6.67 (d, J=8.5 Hz, 1H), 5.07-5.02 (m, 1H), 4.92 (t, J=11.5 Hz, 1H), 4.78 (d, J=50.0 Hz, 1H), 4.30-4.20 (m, 1H), 4.05-3.99 (m, 1H), 3.94-3.90 (m, 1H), 3.73-3.50 (m, 7H), 1.92-1.80 (m, 1H), 1.75-1.70 (m, 1H).
Sources & evidence
- ORD record
- ord-c82a85895ddb4c52b3a4558b63f82d0b
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09388171B2
Reaction notes
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