2-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)- → 3-(3-fluoro-4-((2-(piperidin-1-yl)ethyl)amino)phenyl)-2,6-dimethyl-pyrimidin-4(3H)-one

HRID 56189

Reaction equation

HRID 56189 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][CH2:15][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][CH2:15][CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 57053602-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)-HCID 16682925TrimethylaluminumHCID 549680042-fluoro-N1-(2-(piperidin-1-yl)ethyl)benzene-1,4-diamine

Product 1

HCID 729500053-(3-fluoro-4-((2-(piperidin-1-yl)ethyl)amino)phenyl)-2,6-dimethyl-pyrimidin-4(3H)-oneYield 5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-fluoro-N1-(2-(piperidin-1-yl)ethyl)benzene-1,4-diamine (1.00 g, 4.21 mmol) in CH2Cl2 (30 mL) was added trimethylaluminium (6.3 mL, 12.6 mmol, 2 M in toluene) slowly. The mixture was stirred at rt for 0.5 h, followed by the addition of a solution of methyl 3-acetaminocrotonate (1.6 g, 10.18 mmol) in CH2Cl2 (8 mL). The reaction mixture was stirred at rt for 24 h, then quenched with saturated NH4Cl aqueous solution and extracted with CH2Cl2 (50 mL×3). 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 (DCM/MeOH (V/V)=20:1) to give the title compound as a pale yellow solid (0.07 g, 5%). The compound was characterized by the following spectroscopic data:

Workup

  1. stirringThe reaction mixture was stirred at rt for 24 h
  2. customquenched with saturated NH4Cl aqueous solution
  3. extractionextracted with CH2Cl2 (50 mL×3)
  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 (DCM/MeOH (V/V)=20:1)

Sources & evidence

ORD record
ord-d63847d5afbd496da4e524cbd75d1849
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Linked notes

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