2-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)- → 3-(3-fluoro-4-((2-morpholinoethyl)amino)phenyl)-2,6-dimethyl pyrimidin-4(3H)-one

HRID 56159Notes

Reaction equation

HRID 56159 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[NH:9][CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.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>[F:1][C:2]1[CH:7]=[C:6]([N:8]2[C:28](=[O:29])[CH:27]=[C:26]([CH3:32])[N:22]=[C:23]2[CH3:25])[CH:5]=[CH:4][C:3]=1[NH:9][CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 57053602-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)-HCID 16682925TrimethylaluminumHCID 176096902-fluoro-N1-(2-morpholinoethyl)benzene-1,4-diamine

Product 1

HCID 729498333-(3-fluoro-4-((2-morpholinoethyl)amino)phenyl)-2,6-dimethyl pyrimidin-4(3H)-oneYield 69.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-fluoro-N1-(2-morpholinoethyl)benzene-1,4-diamine (0.50 g, 2.09 mmol) in CH2Cl2 (20 mL) was added trimethylaluminum (3.2 mL, 6.40 mmol, 2 M in toluene) 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 (0.65 g, 4.13 mmol) in CH2Cl2 (5 mL). The reaction mixture was stirred at rt for 36 h, 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 (EtOAc/MeOH (V/V)=30:1) to give the title compound as a white solid (0.50 g, 24%). The compound was characterized by the following spectroscopic data:

Workup

  1. stirringThe reaction mixture was stirred at rt for 36 h
  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 (EtOAc/MeOH (V/V)=30:1)

Sources & evidence

ORD record
ord-738b2cbda2a04d41a39f2d384bb3c46c
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Reaction notes

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