Potassium Carbonate → Pyrazolo[4,3-h]quinazoline-3-carboxamide, 35

HRID 44634Notes

Reaction equation

HRID 44634 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[C:11]([NH2:15])[CH:12]=[CH:13][CH:14]=2)[CH2:4][CH2:3]1.[CH3:16][NH:17][C:18]([C:20]1[C:24]2[C:25]([CH3:37])([CH3:36])[CH:26](CC)[C:27]3[CH:28]=[N:29][C:30](I)=[N:31][C:32]=3[C:23]=2[N:22]([CH3:38])[N:21]=1)=[O:19].C([O-])([O-])=O.[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].CN(C)C=O>[CH3:16][NH:17][C:18]([C:20]1[C:24]2[C:25]([CH3:36])([CH3:37])[CH2:26][C:27]3[CH:28]=[N:29][C:30]([NH:15][C:11]4[CH:12]=[CH:13][CH:14]=[C:9]([CH2:8][N:5]5[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]5)[CH:10]=4)=[N:31][C:32]=3[C:23]=2[N:22]([CH3:38])[N:21]=1)=[O:19]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 64841863-[(4-Methylpiperazin-1-yl)methyl]anilineHCID 86630222HCID 86630222, compound

Product 1

HCID 44236110Pyrazolo[4,3-h]quinazoline-3-carboxamide, 35Yield 62.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

Pd(OAc)2 (16.34 mg, 0.0728 mmol), (±)-BINAP (45.33 mg, 0.0728 mmol) and dimethylformamide (12 mL) were charged in a round-bottom flask flushed with argon. The mixture was stirred under argon for 30 minutes. Then 3-(4-methyl-piperazin-1-ylmethyl)-phenylamine (448.4 mg, 2.184 mmol), ethyl 8-iodo-1,4,4-trimethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid methylamide (300 mg, 0.728 mmol), K2CO3 (1.508 g, 10.910 mmol) and dimethylformamide (10 mL) were added. The resulting mixture was heated to 80° C. in an oil bath under argon with good stirring for 3 hours. After cooling to room temperature, the reaction mixture was filtered by suction filtration washing with dichloromethane and the filtrate was evaporated to dryness. The crude was purified by flash chromatography on silica gel (eluant; dichloromethane/methanol 95:5) to afford 215 mg (yield 62%) of pure title compound.

Workup

  1. customflushed with argon
  2. stirringwith good stirring for 3 hours
  3. temperatureAfter cooling to room temperature
  4. filtrationthe reaction mixture was filtered by suction filtration
  5. washwashing with dichloromethane
  6. customthe filtrate was evaporated to dryness
  7. customThe crude was purified by flash chromatography on silica gel (eluant; dichloromethane/methanol 95:5)

Sources & evidence

ORD record
ord-46b6f899c1b346f6859ceac5aeae3666
Source dataset
uspto-grants-2013_09
Patent number
US08541429B2

Reaction notes

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