L-Alaninol → 3-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-(3-chloro-4-cyano-phenyl)-(1-methyl-1H-pyrazol-4-yl)-methyl]-amide

HRID 1051379Notes

Reaction equation

HRID 1051379 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:44]1[CH:45]=[N:46][N:47]([CH3:49])[CH:48]=1)[C:35]1[CH:42]=[CH:41][C:38]([C:39]#[N:40])=[C:37]([Cl:43])[CH:36]=1>>[Cl:43][C:37]1[CH:36]=[C:35]([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])[C:44]2[CH:45]=[N:46][N:47]([CH3:49])[CH:48]=2)[CH:42]=[CH:41][C:38]=1[C:39]#[N:40]

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 86712017(S)-4-(Amino(1-methyl-1H-pyrazol-4-yl)methyl)-2-chlorobenzonitrile hydrochloride

Product 1

HCID 867120163-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-(3-chloro-4-cyano-phenyl)-(1-methyl-1H-pyrazol-4-yl)-methyl]-amide

Procedure

3-((3S,4S)-3-Fluoro-tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(S)-(3-chloro-4-cyano-phenyl)-(1-methyl-1H-pyrazol-4-yl)-methyl]-amide (II-59) 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)-4-(amino(1-methyl-1H-pyrazol-4-yl)methyl)-2-chlorobenzonitrile hydrochloride (44). 1H NMR (500 MHz, DMSO-d6) δ 9.39 (d, J=8.0 Hz, 1H), 8.94 (s, 1H), 8.11 (s, 1H), 7.99 (d, J=8.5 Hz, 1H), 7.87 (d, J=9.0 Hz, 1H), 7.81 (s, 1H), 7.63-7.55 (m, 3H), 7.41 (s, 1H), 6.89 (s, 1H), 6.69 (d, J=8.0 Hz, 1H), 6.38 (d, J=8.0 Hz, 1H), 4.78 (d, J=49.5 Hz, 1H), 4.25-4.19 (m, 1H), 4.01 (t, J=13.0 Hz, 1H), 3.93-3.90 (m, 1H), 3.79 (s, 3H), 3.67-3.49 (m, 3H), 1.91-1.83 (m, 1H), 1.73-1.70 (m, 1H); LCMS (ESI) m/z: 519.2 [M+H]+.

Sources & evidence

ORD record
ord-c56e560dd7be425fa272601584cdb943
Source dataset
uspto-grants-2016_07
Patent number
US09388171B2

Reaction notes

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