L-Alaninol → 3-(Tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(R)-1-(4-chloro-3-fluoro-phenyl)-propyl]-amide

HRID 1051363Notes

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.[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([C@H:39]([NH2:42])[CH2:40][CH3:41])=[CH:35][C:34]=1[F:43]>>[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([C@H:39]([NH:42][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])[CH2:40][CH3:41])=[CH:35][C:34]=1[F:43]

Participants

Reactant 4

HCID 80307L-Alaninol

HCID 4192234-Aminotetrahydropyran

HCID 86705486HCID 86705486, compound

HCID 86712001(S)-(3-fluoro-4-methoxy-phenyl)-(1-methylpyrazol-4-yl)methanamine hydrochloride

Product 1

HCID 733355643-(Tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(R)-1-(4-chloro-3-fluoro-phenyl)-propyl]-amide

Procedure

3-(Tetrahydro-pyran-4-ylamino)-isoquinoline-6-carboxylic acid [(R)-1-(4-chloro-3-fluoro-phenyl)-propyl]-amide (II-2) 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 (R)-1-(4-chloro-3-fluoro-phenyl)propan-1-amine hydrochloride (70b). 1H NMR (400 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.87 (d, J=8.2 Hz, 1H), 8.05 (s, 1H), 7.85 (d, J=8.5 Hz, 1H), 7.55 (t, J=8.1 Hz, 1H), 7.51 (d, J=8.5 Hz, 1H), 7.46 (dd, J=10.6, 1.5 Hz, 1H), 7.29 (d, J=8.3 Hz, 1H), 6.74 (s, 1H), 6.51 (d, J=7.9 Hz, 1H), 4.95 (dd, J=14.8, 8.3 Hz, 1H), 3.90 (m, 2H), 3.83 (m, 1H), 3.45 (t, J=10.7 Hz, 2H), 1.92 (m, 2H), 1.89-1.73 (m, 2H), 1.56-1.43 (m, 2H), 0.92 (t, J=7.3 Hz, 3H).

Sources & evidence

ORD record: ord-811ab79bcfa5482185460ca989fe63fe
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09388171B2

Reaction notes

Loading…