2-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)- → 3-(4-(diisobutylamino)-3-fluorophenyl)-2,6-dimethylpyrimidin-4(3H)-one

HRID 56145Notes

Reaction equation

HRID 56145 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[N:9]([CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:10][CH:11]([CH3:13])[CH3:12].C[Al](C)C.[NH:22](/[C:26](/[CH3:32])=[CH:27]\[C:28](OC)=[O:29])[C:23]([CH3:25])=O>C(Cl)Cl>[CH2:10]([N:9]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:3]1[CH:4]=[CH:5][C:6]([N:8]2[C:28](=[O:29])[CH:27]=[C:26]([CH3:32])[N:22]=[C:23]2[CH3:25])=[CH:7][C:2]=1[F:1])[CH:11]([CH3:12])[CH3:13]

Participants

5

Reactant 3

HCID 57053602-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)-HCID 16682925TrimethylaluminumHCID 435878672-fluoro-N1,N1-diisobutylbenzene-1,4-diamine

Product 1

HCID 729496553-(4-(diisobutylamino)-3-fluorophenyl)-2,6-dimethylpyrimidin-4(3H)-oneYield 48.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-fluoro-N1,N1-diisobutylbenzene-1,4-diamine (0.40 g, 1.68 mmol) in CH2Cl2 (20 mL) was added trimethylaluminum (8.4 mL, 8.4 mmol, 1 M in heptane) slowly at rt. The reaction mixture was stirred at rt for 0.5 h, followed by the addition of a solution of methyl 3-acetaminocrotonate (290 mg, 1.85 mmol) in CH2Cl2 (10 mL). The reaction mixture was stirred at rt for 3 days, then quenched with saturated NH4Cl aqueous solution and extracted with CH2Cl2 (100 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:1) to give the title compound as pale yellow oil (280 mg, 48%). The compound was characterized by the following spectroscopic data:

Workup

  1. stirringThe reaction mixture was stirred at rt for 3 days
  2. customquenched with saturated NH4Cl aqueous solution
  3. extractionextracted with CH2Cl2 (100 mL×3)
  4. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:1)

Sources & evidence

ORD record
ord-6bd10640e13e4bdfbbdd05f289b059dd
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Reaction notes

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