Trifluoroacetic acid → HCID 178510346, compound

HRID 2239905Notes

Reaction equation

HRID 2239905 reaction equation
Cl[C:2]1[C:3]([C:27]#[N:28])=[C:4]([N:11](CC2C=CC(OC)=CC=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1.[C@H:29]1([NH2:36])[CH2:34][CH2:33][C@H:32]([NH2:35])[CH2:31][CH2:30]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(O)(C(F)(F)F)=O>CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:35][C@H:32]1[CH2:33][CH2:34][C@H:29]([NH:36][C:2]2[C:3]([C:27]#[N:28])=[C:4]([NH:11][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[N:7]=2)[CH2:30][CH2:31]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 86618525HCID 86618525, compoundHCID 178511674HCID 178511674, compound

Product 1

HCID 178510346HCID 178510346, compoundYield 18.2%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
100 °C

Procedure

In a 1 dram vial was added 6-chloro-8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazine-7-carbonitrile (0.019 g, 0.049 mmol) from (1e), (trans)-cyclohexane-1,4-diamine (0.011 g, 0.097 mmol), cesium carbonate (0.048 g, 0.146 mmol), Pd(OAc)2 (0.547 mg, 2.437 μmol), (R)-(−)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphospine [JOSI-Phos] (1.351 mg, 2.437 μmol) and the solids were pump/purged with argon (3×). Dioxane (1.0 ml, 0.05 M) was added and the reaction was heated at 100° C. overnight. Upon cooling, the mixture was filtered through a frit and the resulting solution was concentrated to dryness. To this residue was added TFA (1.0 ml) and the solution was stirred for 18 hours, concentrated and purified by HPLC to provide the titled compound (0.0031 g, 18% yield) as a TFA salt. 1H NMR (500 MHz, MeOH) δ ppm 7.78 (1H, s), 7.57 (1H, s), 7.43-7.51 (2H, m), 7.31-7.40 (3H, m), 3.77-3.89 (1H, m), 3.06-3.20 (1H, m), 2.18-2.29 (2H, m), 2.09 (2H, m), 1.36-1.62 (4H, m). LC/MS, m/z 348 (M+1). HPLC Rt, 1.78 min. Waters Sunfire C18 column (4.6×50 mm). 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

Workup

  1. customthe solids were pump/purged with argon (3×)
  2. additionDioxane (1.0 ml, 0.05 M) was added
  3. temperatureUpon cooling
  4. filtrationthe mixture was filtered through a frit
  5. concentrationthe resulting solution was concentrated to dryness
  6. additionTo this residue was added TFA (1.0 ml)
  7. concentrationconcentrated
  8. custompurified by HPLC

Sources & evidence

ORD record
ord-179ac1b5e4574e97a37c08a3606d1c3d
Source dataset
uspto-grants-2010_05
Patent number
US07723336B2

Reaction notes

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