3-(4-Fluoroisoquinolin-3-yl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine trihydrochloride → 3-(5-Chloro-8-fluoroisoquinolin-3-yl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine trihydrochloride

HRID 1926257Notes

Reaction equation

HRID 1926257 reaction equation
[ClH:1].Cl.Cl.FC1C2C(=CC=CC=2)C=NC=1C1C(N)=NC=C(C2C=NN(C3CCNCC3)C=2)C=1.C(OC([N:40]1[CH2:45][CH2:44][CH:43]([N:46]2[CH:50]=[C:49]([C:51]3[CH:52]=[N:53][C:54]([NH2:69])=[C:55]([C:57]4[N:58]=[CH:59][C:60]5[C:65]([CH:66]=4)=[C:64]([Cl:67])[CH:63]=[CH:62][C:61]=5[F:68])[CH:56]=3)[CH:48]=[N:47]2)[CH2:42][CH2:41]1)=O)(C)(C)C>>[ClH:67].[ClH:1].[ClH:67].[Cl:67][C:64]1[CH:63]=[CH:62][C:61]([F:68])=[C:60]2[C:65]=1[CH:66]=[C:57]([C:55]1[C:54]([NH2:69])=[N:53][CH:52]=[C:51]([C:49]3[CH:48]=[N:47][N:46]([CH:43]4[CH2:42][CH2:41][NH:40][CH2:45][CH2:44]4)[CH:50]=3)[CH:56]=1)[N:58]=[CH:59]2

Participants

3

Reactant 2

HCID 675205253-(4-Fluoroisoquinolin-3-yl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine trihydrochlorideHCID 675207684-{4-[6-Amino-5-(5-chloro-8-fluoroisoquinolin-3-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 675209353-(5-Chloro-8-fluoroisoquinolin-3-yl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine trihydrochloride

Procedure

The procedure for the preparation of 3-(4-fluoroisoquinolin-3-yl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine trihydrochloride was followed, except using 4-{4-[6-amino-5-(5-chloro-8-fluoroisoquinolin-3-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester in place of 4-{4-[6-amino-5-(4-fluoroisoquinolin-3-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester. This afforded the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ=2.11-2.28 (m, 4H), 3.01-3.17 (m, 2H), 3.32-3.47 (m, 2H), 4.47-4.60 (m, 1H), 7.66 (dd, J=9.85, 8.59 Hz, 1H), 8.08-8.15 (m, 2H), 8.34-8.51 (m, 3H), 8.56 (s, 1H), 8.77 (d, J=2.02 Hz, 1H), 9.00 (br. s., 1H), 9.16 (br. s., 1H), 9.67 (s, 1H). 1H NMR (400 MHz, CD3OD): δ=2.29-2.44 (m, 4H), 3.20-3.30 (m, 2H), 3.60 (d, J=12.6 Hz, 2H), 4.54-4.66 (m, 1H), 7.39 (t, J=9.1 Hz, 1H), 7.91 (dd, J=8.3, 4.8 Hz, 1H), 7.94 (s, 1H), 8.14 (s, 1H), 8.18 (s, 1H), 8.29 (s, 1H), 8.43 (s, 1H), 9.61 (s, 1H). MS (ES+): m/z=339.76/341.64 [MH+]. HPLC: tR=2.27 min (ZQ2, polar—5 min).

Sources & evidence

ORD record
ord-99ee5b9806c94487bf50911ca98e01de
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

Loading…