2-Bromothiazole → HCID 57505460, compound

HRID 1663700Notes

Reaction equation

HRID 1663700 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([O:10][C:11]3[CH:12]=[C:13]([NH:17][C:18](=[O:29])[C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=4)[CH:14]=[CH:15][CH:16]=3)=[N:6][N:5]2[CH:30]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].Br[C:80]1[S:81][CH:82]=[CH:83][N:84]=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C.CN(C)C(=O)C>[S:81]1[CH:82]=[CH:83][N:84]=[C:80]1[NH:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([O:10][C:11]3[CH:12]=[C:13]([NH:17][C:18](=[O:29])[C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=4)[CH:14]=[CH:15][CH:16]=3)=[N:6][N:5]2[CH:30]=1

Participants

8

Reactant 4

HCID 764302-BromothiazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 57385788N-{3-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-3-(trifluoromethyl)benzamide

Product 1

HCID 57505460HCID 57505460, compoundYield 5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of N-{3-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-3-(trifluoromethyl)benzamide (165 mg, 0.4 mmol), tris(dibenzylideneacetone)dipalladium (0) (37 mg, 0.04 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (46 mg, 0.03 mmol), sodium t-butoxide (77 mg, 0.8 mmol), 2-bromothiazole (98 mg, 0.6 mmol) and N,N-dimethylacetamide (2 mL) was heated to 70° C. under nitrogen atmosphere, and the mixture was stirred for 2 hr. After allowing the reaction mixture to cool to room temperature, ethyl acetate was added to the mixture, and the mixture was washed with saturated aqueous sodium hydrogencarbonate solution, dried over anhydrous magnesium sulfate, and filtrated. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/19→ethyl acetate alone) to give the title compound (10 mg, 5%) as a light blue solid.

Workup

  1. temperatureto cool to room temperature
  2. washthe mixture was washed with saturated aqueous sodium hydrogencarbonate solution
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltrated
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/19→ethyl acetate alone)

Sources & evidence

ORD record
ord-89e7c9dcf65c4658b5a13e49c9ed8a23
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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