4-(4-Methylpiperazin-1-yl)aniline → HCID 22124616, compound

HRID 1857962Notes

Reaction equation

HRID 1857962 reaction equation
F[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:14])[N:9]2[CH2:12][CH3:13])=[CH:4][N:3]=1.[CH3:15][N:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:28]=[CH:27][C:25]([NH2:26])=[CH:24][CH:23]=2)[CH2:18][CH2:17]1.C([N-]C(C)C)(C)C.[Li+]>C1COCC1.C(O)(=O)C>[CH2:12]([N:9]1[C:10]2[C:5](=[CH:4][N:3]=[C:2]([NH:26][C:25]3[CH:24]=[CH:23][C:22]([N:19]4[CH2:18][CH2:17][N:16]([CH3:15])[CH2:21][CH2:20]4)=[CH:28][CH:27]=3)[CH:11]=2)[CH:6]=[CH:7][C:8]1=[O:14])[CH3:13]

Participants

6

Reactant 3

HCID 7372534-(4-Methylpiperazin-1-yl)anilineHCID 2724682Lithium diisopropylamideHCID 22124621HCID 22124621, compound

Product 1

HCID 22124616HCID 22124616, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of (XV, where R2 is ethyl) (100 mg, 0.52 mmol), 4-(4-methyl-1-piperazinyl)aniline (0.26 g, 1.12 mmol) in THF (5.0 mL) under nitrogen at -78° C. was treated was treated with a solution (0.8 mL, 1.2 mmol) of lithium diisopropylamide (1.5 M in cyclohexane), then the temperature was allowed to rise slowly to 20° C. overnight. The resulting solution was treated with 3 drops of glacial acetic acid and concentrated to a dark residue that was purified by silica gel chromatography eluting with 90:9:1 EtOAc:MeOH:NH4OH. The product fractions were pooled and concentrated to a solid that was triturated in boiling hexanes. The solid was collected and crystallized to give 1-ethyl-7-[4-(4-methylpiperazin-1-yl)phenylamino]-1H-[1,6]naphthyridin-2-one (84 mg, 44%): mp (CH2Cl2 /hexanes) 188-189° C.

Workup

  1. concentrationconcentrated to a dark residue that
  2. customwas purified by silica gel chromatography
  3. washeluting with 90:9:1 EtOAc
  4. concentrationconcentrated to a solid
  5. customthat was triturated
  6. customThe solid was collected
  7. customcrystallized

Sources & evidence

ORD record
ord-053ac18a15374ac09b5cf39689dbb3f0
Source dataset
uspto-grants-2000_11
Patent number
US06150359

Reaction notes

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