Dimethylacetamide → HCID 68483194, compound

HRID 2239898Notes

Reaction equation

HRID 2239898 reaction equation
Cl[C:2]1[CH:3]=[C:4]([N:11]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=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[C:28]([N:30](C)C)=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Zn]>[CH3:26][O:25][C:22]1[CH:23]=[CH:24][C:19]([CH2:18][N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:4]2[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[N:7]=[C:2]([C:28]#[N:30])[CH:3]=2)=[CH:20][CH:21]=1

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 596245586-chloro-N-(4-methoxybenzyl)-N-phenylimidazo[1,2-b]pyridazin-8-amine

Product 1

HCID 68483194HCID 68483194, compoundYield 98%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
150 °C

Procedure

To a 20 ml microwave vial was added 6-chloro-N-(4-methoxybenzyl)-N-phenylimidazo[1,2-b]pyridazin-8-amine (0.66 g, 1.8 mmol) from Example XXXI, step (1a), zinc cyanide (0.13 g, 1.1 mmol), Pd2(dba)3 (0.033 g, 0.036 mmol), 1,1′-bis(diphenylphosphino)-ferrocene [dppf] (0.040 g, 0.07 mmol), zinc dust (0.012 g, 0.18 mmol) and DMA (11.0 ml, 0.17 M). The reaction mixture was sealed and pump/purged 3× with nitrogen then heated in a microwave for 20 minutes at 150° C. Upon cooling, the suspension was diluted with ethyl acetate (50 ml) and filtered through a plug of celite. To the resulting solution was added 10% LiCl solution and the layers separated. The organic layer was washed two additional times with 10% LiCl solution, then brine (1×), dried over Na2SO4, filtered and concentrated in vacuo. This residue was purified on silica gel (ISCO—80 gram) using a 30-100% ethyl acetate/heptane gradient over 20 minutes. To provide 8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazine-6-carbonitrile (0.63 g, 98%). m/z=(357, M+1).

Workup

  1. customThe reaction mixture was sealed
  2. custompump/purged 3× with nitrogen
  3. temperatureUpon cooling
  4. additionthe suspension was diluted with ethyl acetate (50 ml)
  5. filtrationfiltered through a plug of celite
  6. additionTo the resulting solution was added 10% LiCl solution
  7. customthe layers separated
  8. washThe organic layer was washed two additional times with 10% LiCl solution
  9. dry with materialbrine (1×), dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThis residue was purified on silica gel (ISCO—80 gram)
  13. customover 20 minutes

Sources & evidence

ORD record
ord-081aa6f4475843f7ad97af1e798b11e6
Source dataset
uspto-grants-2010_05
Patent number
US07723336B2

Reaction notes

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