Hydrochloric Acid → 3-(4-Methylisoquinolin-3-yl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine trihydrochloride

HRID 1926228Notes

Reaction equation

HRID 1926228 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:36])=[C:23]([C:25]4[N:26]=[CH:27][C:28]5[C:33]([C:34]=4[CH3:35])=[CH:32][CH:31]=[CH:30][CH:29]=5)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:37]>O1CCOCC1>[ClH:37].[ClH:37].[ClH:37].[CH3:35][C:34]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[N:26][C:25]=1[C:23]1[C:22]([NH2:36])=[N:21][CH:20]=[C:19]([C:17]2[CH:16]=[N:15][N:14]([CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)[CH:18]=2)[CH:24]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67521084HCID 67521084, compound

Product 1

HCID 675204513-(4-Methylisoquinolin-3-yl)-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine trihydrochloride

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 4-{4-[6-amino-5-(4-methylisoquinolin-3-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (79.1 mg, 0.163 mmol) in 1,4-dioxane (2.0 mL, 26 mmol) was added 4.0 M of HCl in 1,4-dioxane (2.0 mL), and the mixture was stirred at ambient temperature for 3 h. Almost immediately an off-white solid precipitated. The solid was filtered off, washed with MTBE, and dried in vacuo overnight to give the title compound as an off-white solid. It appeared to be slightly hygroscopic during the filtration; however, after the washing and initial drying it appeared to be non-hygroscopic. 1H NMR (400 MHz, DMSO-d6): δ=14.6 (very brs, 1H), 9.68 (s, 1H), 9.37-9.24 (brm, 1H), 9.24-9.10 (brm, 1H), 8.55 (d, J=2.0 Hz, 1H), 8.47 (d, J=7.6 Hz, 1H), 8.46 (d, J=2.0 Hz, 1H), 8.39 (s, 1H), 8.38 (d, J=7.6 Hz, 1H), 8.14 (t, J=7.2 Hz, 1H), 8.05 (s, 1H), 7.98 (t, J=7.6 Hz, 1H), 7.81 (brs, 2H), 4.54-4.45 (mc, 1H), 3.35 (brd, J=12.6 Hz, 2H), 3.07 (brq, J=11.2 Hz, 2H), 2.59 (s, 3H), 2.26-2.09 (m, 4H). MS(ES+): m/z=385.17 (96) [MH+], 302.1 (100) [MH+-piperidine]. HPLC: tR=0.65 & 1.72 min (peak splitting; polar—5 min, ZQ3).

Workup

  1. customAlmost immediately an off-white solid precipitated
  2. filtrationThe solid was filtered off
  3. washwashed with MTBE
  4. customdried in vacuo overnight

Sources & evidence

ORD record
ord-fd15680b80284cbbb800a8413be7bb6a
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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