Hydrochloric Acid → 6-(3-(4-fluorobenzyloxy)pyridin-4-yl)-3-methyl-2-(morpholin-4-yl)-3H-pyrimidin-4-one hydrochloride

HRID 1091399Notes

Reaction equation

HRID 1091399 reaction equation
[N:1]1([C:7]2[N:12]([CH3:13])[C:11](=[O:14])[CH:10]=[C:9]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][C:16]=3F)[N:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[F:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][OH:28])=[CH:25][CH:24]=1.[H-].[Na+].[ClH:33]>O1CCCC1.CO>[ClH:33].[F:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][O:28][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][C:15]=2[C:9]2[N:8]=[C:7]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[N:12]([CH3:13])[C:11](=[O:14])[CH:10]=2)=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 680224-Fluorobenzylic alcoholHCID 578777672-(morpholin-4-yl)-3-methyl-6-(3-fluoropyridin-4-yl)-3H-pyrimidin-4-one

Product 1

HCID 665947526-(3-(4-fluorobenzyloxy)pyridin-4-yl)-3-methyl-2-(morpholin-4-yl)-3H-pyrimidin-4-one hydrochlorideYield 31%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(morpholin-4-yl)-3-methyl-6-(3-fluoropyridin-4-yl)-3H-pyrimidin-4-one (0.60 g, 2.07 mmol), and 4-fluorobenzyl alcohol (3.3 g, 26.2 mmol) in tetrahydrofuran (15 ml) was added sodium hydride (1.03 g, 2.58 mmol) at 0° C. After stirring at 60° C. for 5 hours, the resulting suspension was partitioned between chloroform and brine and the aqueous layer was extracted with chloroform. The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting 5-10% methanol in chloroform to furnish colorless oil. The methanol (10 ml) solution of resulting oil was treated with 4N hydrochloric acid (5 ml). The residue obtained by evaporation was washed by ethyl acetate to furnish 6-(3-(4-fluorobenzyloxy)pyridin-4-yl)-3-methyl-2-(morpholin-4-yl)-3H-pyrimidin-4-one hydrochloride (0.23 g, 0.53 mmol, 31%) as white crystals.

Workup

  1. customthe resulting suspension was partitioned between chloroform and brine
  2. extractionthe aqueous layer was extracted with chloroform
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography
  7. washeluting 5-10% methanol in chloroform
  8. customto furnish colorless oil
  9. customThe residue obtained by evaporation
  10. washwas washed by ethyl acetate

Sources & evidence

ORD record
ord-7b91d55a3c1e4fdcae1284fecb15cd08
Source dataset
uspto-grants-2012_03
Patent number
US08129377B2

Reaction notes

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