2-(Dicyclohexylphosphino)biphenyl → Tert-butyl (6-(3-methylisothiazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate

HRID 219065Notes

Reaction equation

HRID 219065 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[N:9][N:10]=2)[N:7]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[CH3:45][C:46]1[CH:50]=[C:49]([Sn](C)(C)C)[S:48][N:47]=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].CN(C=O)C>[CH3:45][C:46]1[CH:50]=[C:49]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[N:9][N:10]=3)[N:7]=2)[S:48][N:47]=1

Participants

6

Reactant 3

HCID 27342162-(Dicyclohexylphosphino)biphenyl2×HCID 100383203-Methyl-5-(trimethylstannyl)isothiazoleHCID 57691389tert-Butyl ((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)carbamate

Product 1

HCID 57690989Tert-butyl (6-(3-methylisothiazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamateYield 30%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A pressure vessel was purged with Ar and charged with tert-butyl (6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (5.00 g, 17.6 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.807 g, 0.881 mmol), 2-dicyclohexylphosphinobiphenyl (0.618 g, 1.76 mmol). DMF (50 mL) was added, immediately followed by 3-methyl-5-(trimethylstannyl)isothiazole (6.46 g, 24.7 mmol). The reaction mixture was stirred at 100° C. for 1 h. Two more portions of tris(dibenzylideneacetone)dipalladium(0) (0.807 g, 0.881 mmol) and 2-dicyclohexylphosphinobiphenyl (0.618 g, 1.76 mmol) were added every hour for the first two hours of stirring. Reaction was then stirred was at 100° C. overnight, cooled to room temperature and concentrated in vacuo. Purification by MPLC (EtOAC/MeOH: 100/0 to 90/10) afforded the title compound (1.80 g, 30% yield). MS m/z=347.1 [M+H]+. Calc'd for C15H18N6O2S: 346.41

Workup

  1. customA pressure vessel was purged with Ar
  2. stirringof stirring
  3. customReaction
  4. stirringwas then stirred
  5. waitwas at 100° C. overnight
  6. temperaturecooled to room temperature
  7. concentrationconcentrated in vacuo
  8. customPurification by MPLC (EtOAC/MeOH: 100/0 to 90/10)

Sources & evidence

ORD record
ord-efc8f189880d45df96d4aee9be303ddb
Source dataset
uspto-grants-2012_06
Patent number
US08198448B2

Reaction notes

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