Sodium Bicarbonate → HCID 57505677, compound

HRID 1663940Notes

Reaction equation

HRID 1663940 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])[N:10]=2)[N:7]=1.[NH2:17][C:18]1[CH:19]=[C:20]([NH:24][C:25]([C:27]2[N:31]([CH3:32])[N:30]=[C:29]([CH3:33])[CH:28]=2)=[O:26])[CH:21]=[CH:22][CH:23]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[K+].C(=O)([O-])O.[Na+]>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].C(OCC)(=O)C.O1CCCC1.C(O)(C)(C)C>[CH:14]1([C:12]([NH:11][C:9]2[N:10]=[C:5]3[CH:4]=[CH:3][C:2]([NH:17][C:18]4[CH:19]=[C:20]([NH:24][C:25]([C:27]5[N:31]([CH3:32])[N:30]=[C:29]([CH3:33])[CH:28]=5)=[O:26])[CH:21]=[CH:22][CH:23]=4)=[N:7][N:6]3[CH:8]=2)=[O:13])[CH2:16][CH2:15]1

Participants

9

Reactant 5

HCID 516892Sodium BicarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23665647Potassium tert-butoxideHCID 57386058N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamideHCID 57441034HCID 57441034, compound

Product 1

HCID 57505677HCID 57505677, compoundYield 9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6386tert-ButanolSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Procedure

A mixture of N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (330 mg, 1.0 mmol), N-(3-aminophenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide (280 mg, 1.2 mmol), tris(dibenzylideneacetone)dipalladium (0) (46 mg, 0.050 mmol), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (48 mg, 0.10 mmol), potassium tert-butoxide (170 mg, 1.5 mmol) and tert-butanol was heated under reflux for 2 days. Ethyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogencarbonate solution were added to the mixture, the aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×4). Combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=30/70→100/0) to give the title compound (37 mg, 9%) as a brown solid.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 2 days
  3. extractionthe aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×4)
  4. washCombined organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltrated
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=30/70→100/0)

Sources & evidence

ORD record
ord-2c5b57b3134b41daa605d7e4ade382fc
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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