1-Ethylpiperazine → 8-[[5-(4-Ethyl-1-piperazinyl)-2-(trifluoromethoxy)phenyl]amino]-4,5-dihydro-1-methyl-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide

HRID 1914741Notes

Reaction equation

HRID 1914741 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.[F:29][C:30]([F:58])([F:57])[O:31][C:32]1[CH:37]=[CH:36][C:35](Br)=[CH:34][C:33]=1[NH:39][C:40]1[N:49]=[CH:48][C:47]2[CH2:46][CH2:45][C:44]3[C:50]([C:54]([NH2:56])=[O:55])=[N:51][N:52]([CH3:53])[C:43]=3[C:42]=2[N:41]=1.[Li]N([Si](C)(C)C)[Si](C)(C)C.[CH2:69]([N:71]1[CH2:76][CH2:75][NH:74][CH2:73][CH2:72]1)[CH3:70]>C1COCC1.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:71]1[CH2:76][CH2:75][N:74]([C:35]2[CH:36]=[CH:37][C:32]([O:31][C:30]([F:58])([F:57])[F:29])=[C:33]([NH:39][C:40]3[N:49]=[CH:48][C:47]4[CH2:46][CH2:45][C:44]5[C:50]([C:54]([NH2:56])=[O:55])=[N:51][N:52]([CH3:53])[C:43]=5[C:42]=4[N:41]=3)[CH:34]=2)[CH2:73][CH2:72]1)[CH3:70]

Participants

7

Reactant 4

HCID 791961-EthylpiperazineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 59454336HCID 59454336, compoundHCID 178418261HCID 178418261, compound

Product 1

HCID 529433108-[[5-(4-Ethyl-1-piperazinyl)-2-(trifluoromethoxy)phenyl]amino]-4,5-dihydro-1-methyl-1H-pyrazolo[4,3-h]quinazoline-3-carboxamideYield 52%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Tris(dibenzilideneacetone)dipalladium, Pd2(dba)3, (9.1 mg, 0.01 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)-biphenyl (7.8 mg, 0.02 mmol), 8-[2-trifluoromethoxy-5-bromo-phenylamino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (200 mg, 0.41 mmol) in THF (4.5 mL) were charged in a round-bottom flask flushed with argon. The flask was evacuated and backfilled with argon. LiN(TMS)2 solution (1M in THF, 2.7 mL) and N-ethylpiperazine (0.125 mL, 0.98 mmol) were added and the reaction mixture refluxed for 3 h. The reaction mixture was then allowed to cool to room temperature and concentrated. The crude solid was purified by flash chromatography on silica gel (eluant: DCM/EtOH 90/10) to afford 46 mg (52% yield) of the title compound.

Workup

  1. customflushed with argon
  2. customThe flask was evacuated
  3. temperaturethe reaction mixture refluxed for 3 h
  4. concentrationconcentrated
  5. customThe crude solid was purified by flash chromatography on silica gel (eluant: DCM/EtOH 90/10)

Sources & evidence

ORD record
ord-21fbdbbc77614b788993be9f3be99bee
Source dataset
uspto-grants-2013_12
Patent number
US08614220B2

Reaction notes

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