Toluene → 3-(4-(dihexylamino)-3-fluorophenyl)-2-((3-fluorophenoxy)methyl)-6-methyl-pyrimidin-4(3H)-one

HRID 56279Notes

Reaction equation

HRID 56279 reaction equation
[CH2:1]([N:7]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:20])[CH2:16][C:17](=O)[CH3:18])=[CH:10][C:9]=1[F:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[F:28][C:29]1[CH:30]=[C:31]([CH:37]=[CH:38][CH:39]=1)[O:32][CH2:33][C:34]([NH2:36])=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]>[CH2:1]([N:7]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[C:8]1[CH:13]=[CH:12][C:11]([N:14]2[C:15](=[O:20])[CH:16]=[C:17]([CH3:18])[N:36]=[C:34]2[CH2:33][O:32][C:31]2[CH:37]=[CH:38][CH:39]=[C:29]([F:28])[CH:30]=2)=[CH:10][C:9]=1[F:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]

Participants

7

Reactant 4

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 189381052-(3-Fluorophenoxy)acetamideHCID 90023627N-(4-(dihexylamino)-3-fluorophenyl)-3-oxobutanamide

Product 1

HCID 900229913-(4-(dihexylamino)-3-fluorophenyl)-2-((3-fluorophenoxy)methyl)-6-methyl-pyrimidin-4(3H)-oneYield 26.3%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 7237O-XyleneSolvent

Conditions

Temperature
165 °C

Procedure

To a mixture of N-(4-(dihexylamino)-3-fluorophenyl)-3-oxobutanamide (2.67 g, 7.05 mmol), and 2-(3-fluorophenoxy)acetamide (2.37 g, 14.0 mmol) in xylene (20 mL) was added titanium tetraisopropanolate (5.97 g, 21.0 mmol) and the mixture was stirred at 165° C. for 24 h. The mixture was cooled to rt and 120 mL of toluene and 150 mL of saturated NH4Cl aqueous solution were added. The resulting mixture stirred at rt overnight and filtered and the filtrate was extracted with DCM (150 mL×3). The combined organic layers 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 yellow solid (0.95 g, 26%). 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 (150 mL×3)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=2:1)

Sources & evidence

ORD record
ord-9902e8b2ed2545069c8091b007c15faf
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Reaction notes

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