Diisopropylethylamine → 3-(3-fluoro-4-nitro-phenylsulfanyl)-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine

HRID 1890921Notes

Reaction equation

HRID 1890921 reaction equation
[F:1][C:2]1[CH:3]=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].C(N(C(C)C)CC)(C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:70][N:71]1[CH:75]=[C:74]([C:76]2[CH:77]=[CH:78][C:79]3[N:80]([C:82]([SH:85])=[N:83][N:84]=3)[N:81]=2)[CH:73]=[N:72]1>CN(C=O)C.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]>[F:1][C:2]1[CH:3]=[C:4]([S:85][C:82]2[N:80]3[N:81]=[C:76]([C:74]4[CH:73]=[N:72][N:71]([CH3:70])[CH:75]=4)[CH:77]=[CH:78][C:79]3=[N:84][N:83]=2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 219987353-Fluoro-4-nitrophenyl trifluoromethanesulfonateHCID 178480034HCID 178480034, compound

Product 1

HCID 579110323-(3-fluoro-4-nitro-phenylsulfanyl)-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazineYield 24.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of trifluoro-methanesulfonic acid 3-fluoro-4-nitro-phenyl ester (1.51 g, 4.74 mmol), diisopropylethylamine (1.5 mL, 8.62 mmol) in DMF (14 mL) under nitrogen was degassed by bubbling in nitrogen for 10 min. Tris(dibenzylideneacetone)dipalladium (99 mg, 0.108 mmol, Strem catalyst) and Xantphos (125 mg, 0.215 mmol) were added together in one portion, followed by 6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (1.0 g, 4.31 mmol). The reaction mixture was stirred at 100° C. for 3 h, then it was concentrated in vacuo. The residue was partitioned between saturated aqueous ammonium chloride and 10% methanol in dichloromethane. The aqueous layer was extracted with 10% methanol in dichloromethane, and the combined organic layers were directly adsorbed on silica gel. Purification by flash chromatography on silica gel using a gradient of 0-10% methanol/dichloromethane afforded 387 mg of 3-(3-fluoro-4-nitro-phenylsulfanyl)-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine as a yellow solid (24% yield): 1H NMR (DMSO-d6) δ 3.90 (s, 3H), 7.20 (dd, 1H), 7.59 (dd, 1H), 7.87 (d, 1H), 8.06 (m, 2H), 8.46 (s, 1H), 8.54 (d, 1H); MS (m/z) 372 [M+H]+.

Workup

  1. customby bubbling in nitrogen for 10 min
  2. concentrationit was concentrated in vacuo
  3. customThe residue was partitioned between saturated aqueous ammonium chloride and 10% methanol in dichloromethane
  4. extractionThe aqueous layer was extracted with 10% methanol in dichloromethane
  5. customPurification by flash chromatography on silica gel using a gradient of 0-10% methanol/dichloromethane

Sources & evidence

ORD record
ord-afa71f959f32491e9a17bf3168c503c5
Source dataset
uspto-grants-2013_08
Patent number
US08507489B2

Reaction notes

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