Toluene → 3-(3-chloro-4-morpholinophenyl)-2-((3-fluorophenoxy)methyl)-6-methylpyrimidin-4(3H)-one

HRID 56280Notes

Reaction equation

HRID 56280 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:14][C:15](=[O:20])[CH2:16][C:17](=O)[CH3:18])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[F:21][C:22]1[CH:23]=[C:24]([CH:30]=[CH:31][CH:32]=1)[O:25][CH2:26][C:27]([NH2:29])=O.C1(C)C=CC=CC=1.[NH4+].[Cl-]>C1(C)C(C)=CC=CC=1.C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.[Ti+4]>[Cl:1][C:2]1[CH:3]=[C:4]([N:14]2[C:15](=[O:20])[CH:16]=[C:17]([CH3:18])[N:29]=[C:27]2[CH2:26][O:25][C:24]2[CH:30]=[CH:31][CH:32]=[C:22]([F:21])[CH:23]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 189381052-(3-Fluorophenoxy)acetamideHCID 90022603N-(3-chloro-4-morpholinophenyl)-3-oxobutanamide

Product 1

HCID 900516683-(3-chloro-4-morpholinophenyl)-2-((3-fluorophenoxy)methyl)-6-methylpyrimidin-4(3H)-oneYield 23%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 7237O-XyleneSolvent

Conditions

Temperature
165 °C

Procedure

A mixture of N-(3-chloro-4-morpholinophenyl)-3-oxobutanamide (0.89 g, 3.00 mmol), 2-(3-fluorophenoxy)acetamide (1.01 g, 5.97 mmol) and titanium tetraisopropanolate (7.2 mL) in xylene (20 mL) was stirred at 165° C. for 24 h. The mixture was cooled to rt and 45 mL of toluene and 60 mL of saturated NH4Cl aqueous solution were added. The resulting mixture stirred at rt overnight and filtered and the filtrate was extracted with DCM (60 mL×3). The combined organic layers were washed with brine, 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 a yellow solid (0.29 g, 23%). The compound was characterized by the following spectroscopic data:

Workup

  1. temperatureThe mixture was cooled to rt
  2. stirringThe resulting mixture stirred at rt overnight
  3. filtrationfiltered
  4. extractionthe filtrate was extracted with DCM (60 mL×3)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:1)

Sources & evidence

ORD record
ord-5afc67fde7fe4768a638b29ddf6c10a9
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Reaction notes

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