3-Fluoro-4-morpholinoaniline → 3-(3-fluoro-4-morpholinophenyl)-2-(3-fluorophenethyl)-6-methyl-pyrimidin-4(3H)-one

HRID 56249

Reaction equation

HRID 56249 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][O:12][CH2:11][CH2:10]1)[NH2:5].C[Al](C)C.C[O:20][C:21](=O)/[CH:22]=[C:23](\[NH:25][C:26](=O)[CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[CH:30]=1)/[CH3:24]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([N:5]2[C:21](=[O:20])[CH:22]=[C:23]([CH3:24])[N:25]=[C:26]2[CH2:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[CH:30]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1

Participants

5

Reactant 3

HCID 14853303-Fluoro-4-morpholinoanilineHCID 16682925TrimethylaluminumHCID 90023034(Z)-methyl 3-(3-(3-fluorophenyl)propanamido)but-2-enoate

Product 1

HCID 729494773-(3-fluoro-4-morpholinophenyl)-2-(3-fluorophenethyl)-6-methyl-pyrimidin-4(3H)-oneYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-fluoro-4-morpholinoaniline (1.10 g, 5.61 mmol) in DCM (20 mL) was added trimethylaluminium (5.7 mL, 11.4 mmol, 2 M in toluene) and the mixture was stirred at rt for 0.5 h. A solution of (Z)-methyl-3-(3-(3-fluorophenyl)propanamido)but-2-enoate (1.00 g, 3.77 mmol) in DCM (8 mL) was added slowly and the resulting mixture was stirred at rt for 24 h. The mixture was then quenched with saturated NH4Cl aqueous solution and extracted with CH2Cl2 (50 mL×2). The combined organic phases were washed with brine (100 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc) to give the title compound as an orange solid (1.10 g, 71%). The compound was characterized by the following spectroscopic data:

Workup

  1. stirringthe resulting mixture was stirred at rt for 24 h
  2. customThe mixture was then quenched with saturated NH4Cl aqueous solution
  3. extractionextracted with CH2Cl2 (50 mL×2)
  4. washThe combined organic phases were washed with brine (100 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (EtOAc)

Sources & evidence

ORD record
ord-9e76523cfb174dee959c94ac4552d2de
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Linked notes

Loading…