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

HRID 1051378Notes

Reaction equation

HRID 1051378 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]([Cl:43])=[C:39]([F:44])[CH:38]=1)[CH2:35][OH:36]>>[Cl:43][C:40]1[CH:41]=[CH:42][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:38][C:39]=1[F:44]

Participants

5

Reactant 4

HCID 80307L-AlaninolHCID 68295107(3S,4S)-3-fluorotetrahydro-2H-pyran-4-amineHCID 86712001(S)-(3-fluoro-4-methoxy-phenyl)-(1-methylpyrazol-4-yl)methanamine hydrochlorideHCID 86712006(S)-2-Amino-2-(4-chloro-3-fluorophenyl)ethan-1-ol hydrochloride

Product 1

HCID 867120153-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(4-chloro-3-fluoro-phenyl)-2-hydroxy-ethyl]-amide

Procedure

3-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(4-chloro-3-fluoro-phenyl)-2-hydroxy-ethyl]-amide (II-54) 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-chloro-3-fluoro-phenyl)ethanol hydrochloride (62e). 1H NMR (500 MHz, MeOH-d4): δ 8.90 (s, 1H), 8.09 (s, 1H), 7.92-7.88 (m, 1H), 7.61-7.59 (m, 1H), 7.47-7.45 (m, 1H), 7.38-7.33 (m, 1H), 7.28-7.24 (m, 1H), 6.91 (d, J=9.0 Hz, 1H), 5.21 (t, J=6.5 Hz, 1H), 4.84-4.73 (m, 1H), 4.27-4.11 (m, 2H), 4.05-4.02 (m, 1H), 3.92-3.80 (m, 2H), 3.75-3.60 (m, 2H), 2.06-1.96 (m, 1H), 1.93-1.88 (m, 1H).

Sources & evidence

ORD record
ord-876e1ee4e66e494cb1811ca0da70e109
Source dataset
uspto-grants-2016_07
Patent number
US09388171B2

Reaction notes

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