P-Anisidine → HCID 68275989, compound

HRID 1475954Notes

Reaction equation

HRID 1475954 reaction equation
[CH3:1][O:2][C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][CH:4]=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.Br[C:53]1[C:74](/[CH:75]=[CH:76]/[CH2:77][N:78]2[CH2:83][CH2:82][CH2:81][CH2:80][CH2:79]2)=[C:56]2[CH:57]=[C:58]([C:61]([N:63]([CH2:69][CH2:70][CH:71]([CH3:73])[CH3:72])[CH2:64][CH2:65][CH:66]([CH3:68])[CH3:67])=[O:62])[CH:59]=[CH:60][N:55]2[N:54]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.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]>[CH2:69]([N:63]([CH2:64][CH2:65][CH:66]([CH3:68])[CH3:67])[C:61]([C:58]1[CH:59]=[CH:60][N:55]2[N:54]=[C:53]([NH:7][C:6]3[CH:8]=[CH:9][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[C:74]([CH:75]=[CH:76][CH2:77][N:78]3[CH2:79][CH2:80][CH2:81][CH2:82][CH2:83]3)=[C:56]2[CH:57]=1)=[O:62])[CH2:70][CH:71]([CH3:72])[CH3:73]

Participants

8

Reactant 4

HCID 7732P-AnisidineHCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 60141460HCID 60141460, compound

Product 1

HCID 68275989HCID 68275989, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

In a sealed tube 4-methoxyaniline (18.34 mg, 0.149 mmol), tris(dibenzylideneacetone)dipalladium (4.55 mg, 4.97 μmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (5.75 mg, 9.93 μmol) were added to a suspension of (E)-2-bromo-N,N-diisopentyl-3-(3-(piperidin-1-yl)prop-1-en-1-yl)pyrazolo[1,5-a]pyridine-5-carboxamide (50 mg, 0.099 mmol) and potassium phosphate, dibasic (57.1 mg, 0.328 mmol) in toluene (5 ml). The mixture was heated at 110° C. overnight. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate (3×25 mL). The combined organics were washed with brine, dried over anh. sodium sulfate, filtered and concentrated. The residue was purified by SCX (silica-gel supported sulfonic acid) then by preparative HPLC (20% to 100% MeOH in water (0.05% TFA) in 7 minutes) to afford N,N-diisopentyl-2-((4-methoxyphenyl)amino)-3-(3-(piperidin-1-yl)prop-1-en-1-yl)pyrazolo[1,5-a]pyridine-5-carboxamide. LCMS m/z 546.4 (M+H)+ weak, 461.3 (strong); ret. time=2.19 min.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (3×25 mL)
  3. washThe combined organics were washed with brine
  4. dry with materialdried over anh. sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by SCX (silica-gel supported sulfonic acid)

Sources & evidence

ORD record
ord-d441a941112640cab22029b153e48620
Source dataset
uspto-grants-2015_04
Patent number
US09018395B2

Reaction notes

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