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

HRID 1051367Notes

Reaction equation

HRID 1051367 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]([Cl:42])=[C:38]([F:43])[CH:37]=1)[CH2:34][OH:35]>>[Cl:42][C:39]1[CH:40]=[CH:41][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:37][C:38]=1[F:43]

Participants

5

Reactant 4

HCID 80307L-AlaninolHCID 4192234-AminotetrahydropyranHCID 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 733353573-(Tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(4-chloro-3-fluoro-phenyl)-2-hydroxy-ethyl]-amide

Procedure

3-(Tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-1-(4-chloro-3-fluoro-phenyl)-2-hydroxy-ethyl]-amide (II-12) 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-(4-chloro-3-fluoro-phenyl)ethanol hydrochloride (62e). 1H NMR (400 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.83 (d, J=7.9 Hz, 1H), 8.10 (s, 1H), 7.85 (d, J=8.6 Hz, 1H), 7.55 (t, J=8.1 Hz, 1H), 7.53 (dd, J=8.6, 1.6 Hz, 1H), 7.47 (dd, J=10.6, 1.8 Hz, 1H), 7.29 (dd, J=8.3, 1.7 Hz, 1H), 6.74 (s, 1H), 6.53 (d, J=7.9 Hz, 1H), 5.10 (q, J=7.1 Hz, 1H), 5.03 (t, J=5.8 Hz, 1H), 3.94-3.87 (m, 2H), 3.87-3.78 (m, 1H), 3.78-3.64 (m, 2H), 3.45 (td, J=11.5, 2.0 Hz, 2H), 1.92 (d, J=12.4 Hz, 2H), 1.56-1.43 (m, 2H).

Sources & evidence

ORD record
ord-8e044c5a50014a51b37947e5244a2bd8
Source dataset
uspto-grants-2016_07
Patent number
US09388171B2

Reaction notes

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