1-Methylpiperazine → HCID 178480760, compound

HRID 1914763Notes

Reaction equation

HRID 1914763 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.Br[C:30]1[CH:31]=[CH:32][C:33]([O:53][C:54]([F:57])([F:56])[F:55])=[C:34]([NH:36][C:37]2[N:46]=[CH:45][C:44]3[CH2:43][CH2:42][C:41]4[C:47]([C:50]([NH2:52])=[O:51])=[N:48][NH:49][C:40]=4[C:39]=3[N:38]=2)[CH:35]=1.[Li]N([Si](C)(C)C)[Si](C)(C)C.[CH3:68][N:69]1[CH2:74][CH2:73][NH:72][CH2:71][CH2:70]1>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]>[CH3:68][N:69]1[CH2:74][CH2:73][N:72]([C:30]2[CH:31]=[CH:32][C:33]([O:53][C:54]([F:57])([F:56])[F:55])=[C:34]([NH:36][C:37]3[N:46]=[CH:45][C:44]4[CH2:43][CH2:42][C:41]5[C:47]([C:50]([NH2:52])=[O:51])=[N:48][NH:49][C:40]=5[C:39]=4[N:38]=3)[CH:35]=2)[CH2:71][CH2:70]1

Participants

7

Reactant 4

HCID 531671-MethylpiperazineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 178418261HCID 178418261, compoundHCID 178513841HCID 178513841, compound

Product 1

HCID 178480760HCID 178480760, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Tris(dibenzilideneacetone)dipalladium, Pd2(dba)3, (2.3 g, 2.5 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)-biphenyl (950 mg, 2.4 mmol), 8-[5-bromo-2-trifluoromethoxy-phenylamino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (14.8 g, 31.54 mmol) in THF (160 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, 630 mL) and N-methylpiperazine (69 mL, 50.64 mmol) were added and the reaction mixture refluxed for 1 h. The reaction mixture was then allowed to cool to room temperature and filtered through a pad of celite. The organic phase was concentrated. The crude solid was purified by flash chromatography on silica gel (eluant: DCM/MeOH 95/5) to afford 9.2 g (60% yield) of the title compound.

Workup

  1. customflushed with argon
  2. customThe flask was evacuated
  3. temperaturethe reaction mixture refluxed for 1 h
  4. filtrationfiltered through a pad of celite
  5. concentrationThe organic phase was concentrated
  6. customThe crude solid was purified by flash chromatography on silica gel (eluant: DCM/MeOH 95/5)

Sources & evidence

ORD record
ord-1fc197d36e4f47ffbb5ffafaa0eb84ac
Source dataset
uspto-grants-2013_12
Patent number
US08614220B2

Reaction notes

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