Carbonic Acid → 3-(3-fluorophenyl)-2-(hydroxymethyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

HRID 405956Notes

Reaction equation

HRID 405956 reaction equation
Br[C:2]1[C:7](=[O:8])[N:6]2[C:9]([CH3:13])=[CH:10][CH:11]=[CH:12][C:5]2=[N:4][C:3]=1[CH2:14][OH:15].[F:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1.C(O)(O)=O>C(#N)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:16][C:17]1[CH:22]=[C:21]([C:2]2[C:7](=[O:8])[N:6]3[C:9]([CH3:13])=[CH:10][CH:11]=[CH:12][C:5]3=[N:4][C:3]=2[CH2:14][OH:15])[CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 767Carbonic AcidHCID 27339863-Fluorophenylboronic acidHCID 668314003-bromo-2-(hydroxymethyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

Product 1

HCID 668313583-(3-fluorophenyl)-2-(hydroxymethyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
85 °C

Procedure

A mixture of 3-bromo-2-(hydroxymethyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one (0.09450 g, 0.3512 mmol), 3-fluorophenylboronic acid (0.09827 g, 0.7024 mmol), tetrakis(triphenylphosphine)palladium (0.02029 g, 0.01756 mmol), and sodium carbonate anhydrous (0.1861 g, 1.756 mmol) in acetonitrile-water (3:1) (4 mL) was stirred at 85° C. After 2 h, the mixture was cooled to rt and partitioned between EtOAc (50 mL) and water (50 mL). The organic layer was washed with brine (50 mL×2), dried over Na2SO4, filtered, and concd under reduced pressure. The residue was purified by silica gel column chromatography on a 40 g Redi-Sep™ column using 0 to 100% gradient of EtOAc in hexane over 14 min and then 100% isocratic of EtOAc for 20 min as eluent to give 3-(3-fluorophenyl)-2-(hydroxymethyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one as a yellow solid: Mass Spectrum (ESI) m/e=285.1 (M+1).

Workup

  1. temperaturethe mixture was cooled to rt
  2. custompartitioned between EtOAc (50 mL) and water (50 mL)
  3. washThe organic layer was washed with brine (50 mL×2)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customThe residue was purified by silica gel column chromatography on a 40 g Redi-Sep™ column
  7. customover 14 min

Sources & evidence

ORD record
ord-14addec295c44e3eaa8e8198aa936f92
Source dataset
uspto-grants-2014_06
Patent number
US08754089B2

Reaction notes

Loading…