Nitrogen → 3-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-2,6-dimethylpyrimidin-4(3H)-one

HRID 56105Notes

Reaction equation

HRID 56105 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]1)[NH2:5].C[Al](C)C.N#N.[NH:22](/[C:26](/[CH3:32])=[CH:27]\[C:28](OC)=[O:29])[C:23]([CH3:25])=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([N:5]2[C:28](=[O:29])[CH:27]=[C:26]([CH3:32])[N:22]=[C:23]2[CH3:25])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:10][CH2:11][N:12]([CH3:15])[CH2:13][CH2:14]1

Participants

6

Reactant 4

HCID 947NitrogenHCID 27830553-Fluoro-4-(4-methylpiperazin-1-yl)anilineHCID 57053602-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)-HCID 16682925Trimethylaluminum

Product 1

HCID 729483933-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-2,6-dimethylpyrimidin-4(3H)-oneYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-fluoro-4-(4-methylpiperazin-1-yl)aniline (11.01 g, 52.60 mol) in anhydrous CH2Cl2 (200 mL) was added trimethylaluminum (158 mL, 158 mmol, 1.0 M in toluene) slowly under N2. The mixture was stirred at rt for 20 min, followed by the addition of a solution of methyl 3-acetaminocrotonate (9.92 g, 63.10 mmol) in anhydrous CH2Cl2 (20 mL). The reaction mixture was stirred at rt for another 5 h, then quenched with saturated NH4Cl aqueous solution and extracted with CH2Cl2. The combined organic phases were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (CH2Cl2/MeOH (V/V)=5:1) to give the title compound as a white solid (11.31 g, 68%). The compound was characterized by the following spectroscopic data:

Workup

  1. stirringThe reaction mixture was stirred at rt for another 5 h
  2. customquenched with saturated NH4Cl aqueous solution
  3. extractionextracted with CH2Cl2
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (CH2Cl2/MeOH (V/V)=5:1)

Sources & evidence

ORD record
ord-5c0cd64dea8f414489a3944bd966233c
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Reaction notes

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