L-Alaninol → 3-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(3-chloro-4-fluoro-phenyl)-2-hydroxy-ethyl]-amide

HRID 1051377Notes

Reaction equation

HRID 1051377 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]([F:43])=[C:39]([Cl:44])[CH:38]=1)[CH2:35][OH:36]>>[Cl:44][C:39]1[CH:38]=[C:37]([C@H:34]([NH:33][C:3]([C:2]2[CH:5]=[C:24]3[C:18](=[CH:19][CH:20]=2)[CH:31]=[N:29][C:30]([NH:13][C@H:12]2[CH2:11][CH2:10][O:9][CH2:8][C@H:7]2[F:6])=[CH:26]3)=[O:4])[CH2:35][OH:36])[CH:42]=[CH:41][C:40]=1[F:43]

Participants

5

Reactant 4

HCID 80307L-AlaninolHCID 67033315(S)-2-amino-2-(3-chloro-4-fluorophenyl)ethanol hydrochlorideHCID 68295107(3S,4S)-3-fluorotetrahydro-2H-pyran-4-amineHCID 86712001(S)-(3-fluoro-4-methoxy-phenyl)-(1-methylpyrazol-4-yl)methanamine hydrochloride

Product 1

HCID 867120143-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(3-chloro-4-fluoro-phenyl)-2-hydroxy-ethyl]-amide

Procedure

3-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(3-chloro-4-fluoro-phenyl)-2-hydroxy-ethyl]-amide (II-53) 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-(3-chloro-4-fluoro-phenyl)ethanol hydrochloride (62f). 1H NMR (500 MHz, MeOH-d4): δ 8.90 (s, 1H), 8.08 (s, 1H), 7.90 (d, J=8.5 Hz, 1H), 7.60-7.57 (m, 2H), 7.43-7.30 (m, 1H), 7.27-7.23 (m, 1H), 6.93 (s, 1H), 5.21-5.18 (m, 1H), 4.86-4.73 (m, 1H), 4.27-4.12 (m, 2H), 4.05-4.02 (m, 1H), 3.91-3.86 (m, 2H), 3.75-3.62 (m, 2H), 2.04-1.96 (m, 1H), 1.90-1.87 (m, 1H),

Sources & evidence

ORD record
ord-3a8bad83a79a44cb918b67b38212e245
Source dataset
uspto-grants-2016_07
Patent number
US09388171B2

Reaction notes

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