Dimethylformamide → HCID 67076206, compound

HRID 81948Notes

Reaction equation

HRID 81948 reaction equation
C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P([C:41]2[CH:46]=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[NH2:47][C:48]1[CH:63]=[CH:62][C:51]([C:52]([NH:54][CH:55]2[CH2:60][CH2:59]CCN2C)=[O:53])=[CH:50][C:49]=1[O:64][C:65]([F:68])([F:67])[F:66].I[C:70]1[N:79]=[CH:78][C:77]2[CH2:76][CH2:75][C:74]3[C:80]([C:84]([O:86][CH2:87][CH3:88])=[O:85])=[N:81][N:82]([CH3:83])[C:73]=3[C:72]=2[N:71]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:95][N:96](C)C=O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:83][N:82]1[C:73]2[C:72]3[N:71]=[C:70]([NH:47][C:48]4[CH:63]=[CH:62][C:51]([C:52](=[O:53])[NH:54][CH:55]5[CH2:60][CH2:59][N:96]([CH3:95])[CH2:46][CH2:41]5)=[CH:50][C:49]=4[O:64][C:65]([F:66])([F:67])[F:68])[N:79]=[CH:78][C:77]=3[CH2:76][CH2:75][C:74]=2[C:80]([C:84]([O:86][CH2:87][CH3:88])=[O:85])=[N:81]1

Participants

7

Reactant 5

HCID 6228Dimethylformamide2×HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 44232943ethyl 8-iodo-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylateHCID 670760854-amino-N-(1-methylpiperidin-yl)-3-(trifluoromethoxy)benzamide

Product 1

HCID 67076206HCID 67076206, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

Palladium acetate [Pd(OAc)2] (101 mg, 0.45 mmol), (+)-BINAP (280 mg, 0.45 mmol) and dimethylformamide (70 mL) were charged to a round-bottom flask flushed with argon. The flask was evacuated and backfilled with argon. The mixture was stirred under argon for 30 minutes and added to a mixture of 4-amino-N-(1-methylpiperidin-yl)-3-(trifluoromethoxy)benzamide (3.78 g, 12.5 mmol), ethyl 8-iodo-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate (1.6 g, 4.16 mmol), and potassium carbonate (5.74 g, 41.6 mmol) in dimethylformamide (50 mL). The resulting mixture was stirred at 70° C. for 8 hours under argon. After cooling to room temperature, the reaction mixture was filtered on a pad of celite. The solvent was concentrated, the crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/ethanol 9/1) to afford 850 mg (45% yield) of the title compound.

Workup

  1. customflushed with argon
  2. customThe flask was evacuated
  3. stirringThe resulting mixture was stirred at 70° C. for 8 hours under argon
  4. filtrationthe reaction mixture was filtered on a pad of celite
  5. concentrationThe solvent was concentrated
  6. customthe crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/ethanol 9/1)

Sources & evidence

ORD record
ord-b699992743ad45d3bd79a0a811eecd25
Source dataset
uspto-grants-2014_09
Patent number
US08846701B2

Reaction notes

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