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

HRID 56166Notes

Reaction equation

HRID 56166 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][CH2:12][N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C[Al](C)C.[NH:23](/[C:27](/[CH3:33])=[CH:28]\[C:29](OC)=[O:30])[C:24]([CH3:26])=O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([N:8]2[C:29](=[O:30])[CH:28]=[C:27]([CH3:33])[N:23]=[C:24]2[CH3:26])[CH:5]=[CH:4][C:3]=1[NH:9][CH2:10][CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 57053602-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)-HCID 16682925TrimethylaluminumHCID 431684652-fluoro-N1-(3-morpholinopropyl)benzene-1,4-diamine

Product 1

HCID 729498373-(3-fluoro-4-((3-morpholinopropyl)amino)phenyl)-2,6-dimethyl pyrimidin-4(3H)-oneYield 27%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-fluoro-N1-(3-morpholinopropyl)benzene-1,4-diamine (1.60 g, 6.23 mmol) in CH2Cl2 (30 mL) was added trimethylaluminum (22 mL, 44 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 (1.98 g, 12.59 mmol) in CH2Cl2 (10 mL). The reaction was stirred at rt overnight, then quenched with saturated NH4Cl aqueous solution and extracted with CH2Cl2 (50 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)=2:1) to give the title compound as a pale yellow solid (0.60 g, 27%). The compound was characterized by the following spectroscopic data:

Workup

  1. stirringThe reaction was stirred at rt overnight
  2. customquenched with saturated NH4Cl aqueous solution
  3. extractionextracted with CH2Cl2 (50 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)=2:1)

Sources & evidence

ORD record
ord-3d08a77fdffc4890beacb43fc7360032
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Reaction notes

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