Trifluoroacetic acid → N6-(4-Aminocyclohexyl)-N8-phenyl-3-((E)-2-(4-pyridinyl)vinyl)imidazo[1,2-b]pyridazine-6,8-diamine

HRID 2239894Notes

Reaction equation

HRID 2239894 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[CH:10]=[C:11]([N:26](CC3C=CC(OC)=CC=3)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:12]3[N:13]([C:15]([CH:18]=[CH:19][C:20]4[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=4)=[CH:16][N:17]=3)[N:14]=2)[CH2:4][CH2:3]1.C(O)(C(F)(F)F)=O>ClCCl>[NH2:1][CH:2]1[CH2:3][CH2:4][CH:5]([NH:8][C:9]2[CH:10]=[C:11]([NH:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:12]3[N:13]([C:15](/[CH:18]=[CH:19]/[C:20]4[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=4)=[CH:16][N:17]=3)[N:14]=2)[CH2:6][CH2:7]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178490933HCID 178490933, compound

Product 1

HCID 59304414N6-(4-Aminocyclohexyl)-N8-phenyl-3-((E)-2-(4-pyridinyl)vinyl)imidazo[1,2-b]pyridazine-6,8-diamineYield 89.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To N6-(trans-4-aminocyclohexyl)-N8-(4-methoxybenzyl)-N8-phenyl-3-(2-(pyridin-4-yl)vinyl)imidazo[1,2-b]pyridazine-6,8-diamine (30 mg) from step (1c) in dichloromethane at room temperature was added excess TFA. The mixture was stirred for 30 min, concentrated, and the resulting residue was purified by reverse phase preparative HPLC to provide the titled compound as a yellow solid (21 mg). NMR (400 MHz, DMSO-d6) δ ppm 9.05 (1H, s), 8.66 (2H, m), 7.78-7.90 (8H, m), 7.39-7.44 (4H, m), 7.16 (1H, m), 6.68 (1H, m), 6.26 (1H, s), 3.62 (1H, m), 3.08 (1H, m), 2.20 (2H, m), 2.02 (2H, m), 1.51-1.54 (2H, m), 1.25-1.29 (2H, m). LC/MS, m/e 426 (M+1). HPLC Rt, 1.89 min. YMC S5 ODSC18 column (4.6×50 mm). 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.2% H3PO4)—Solvent A: (10% MeOH, 90% H2O, 0.2% H3PO4). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

Workup

  1. concentrationconcentrated
  2. customthe resulting residue was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-59e67b859d45442288321342ed3451cb
Source dataset
uspto-grants-2010_05
Patent number
US07723336B2

Reaction notes

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