Water → 3-(3-fluoro-4-morpholinophenyl)-2-(((5-fluoropyridin-3-yl)oxy)methyl)-6-methyl-pyrimidin-4(3H)-one

HRID 56273Notes

Reaction equation

HRID 56273 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([O:8][CH2:9][C:10]([NH2:12])=O)[CH:5]=[N:6][CH:7]=1.[F:13][C:14]1[CH:15]=[C:16]([NH:26][C:27](=[O:32])[CH2:28][C:29](=O)[CH3:30])[CH:17]=[CH:18][C:19]=1[N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.CCOC(C)=O.O>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]>[F:13][C:14]1[CH:15]=[C:16]([N:26]2[C:27](=[O:32])[CH:28]=[C:29]([CH3:30])[N:12]=[C:10]2[CH2:9][O:8][C:4]2[CH:5]=[N:6][CH:7]=[C:2]([F:1])[CH:3]=2)[CH:17]=[CH:18][C:19]=1[N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 900226812-((5-Fluoropyridin-3-yl)oxy)acetamideHCID 90023295N-(3-fluoro-4-morpholinophenyl)-3-oxobutanamide

Product 1

HCID 900516953-(3-fluoro-4-morpholinophenyl)-2-(((5-fluoropyridin-3-yl)oxy)methyl)-6-methyl-pyrimidin-4(3H)-oneYield 27%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 7237O-XyleneSolvent

Procedure

To a mixture of 2-((5-fluoropyridin-3-yl)oxy)acetamide (200 mg, 1.18 mmol) and N-(3-fluoro-4-morpholinophenyl)-3-oxobutanamide (330 mg, 1.18 mmol) in xylene (10 mL) was added titanium tetraisopropanolate (2.7 mg, 9.5 mmol) and the mixture was refluxed for 50 h. The mixture was cooled to rt and 60 mL of EtOAc and 10 mL of water were added. The resulting mixture was filtered and the filtrate was 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 (130 mg, 27%). The compound was characterized by the following spectroscopic data:

Workup

  1. temperaturethe mixture was refluxed for 50 h
  2. filtrationThe resulting mixture was filtered
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:1)

Sources & evidence

ORD record
ord-2a99ca492f3e4809b414e5c4b7aa3abf
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Reaction notes

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