Morpholine → 2-(morpholin-4-yl)-3-methyl-6-(3-fluoropyridin-4-yl)-3H-pyrimidin-4-one

HRID 1091396Notes

Reaction equation

HRID 1091396 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(N(CC)CC)C.Cl[C:15]1[N:20]([CH3:21])[C:19](=[O:22])[CH:18]=[C:17]([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][C:24]=2[F:29])[N:16]=1>O1CCCC1>[F:29][C:24]1[CH:25]=[N:26][CH:27]=[CH:28][C:23]=1[C:17]1[N:16]=[C:15]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)[N:20]([CH3:21])[C:19](=[O:22])[CH:18]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 8471TriethylamineHCID 595768122-Chloro-3-methyl-6-(3-fluoropyridin-4-yl)-3H-pyrimidin-4-one

Product 1

HCID 578777672-(morpholin-4-yl)-3-methyl-6-(3-fluoropyridin-4-yl)-3H-pyrimidin-4-oneYield 94.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of morpholine (3.2 g, 36.7 mmol) and triethylamine (10.2 g, 101 mmol) in tetrahydrofuran (80 ml) was added 2-chloro-6-(3-fluoropyridin-4-yl)-3-methyl-3H-pyrimidin-4-one (8.0 g, 32.4 mmol) portionwise and stirred for 12 hours. The resulting suspension was partitioned between chloroform and 1N sodium hydroxide 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 6-(3-fluoropyridin-4-yl)-3-methyl-2-(morpholin-4-yl)-3H-pyrimidin-4-one (8.9 g, 30.7 mmol, 92%) as white crystals.

Workup

  1. customThe resulting suspension was partitioned between chloroform and 1N sodium hydroxide
  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

Sources & evidence

ORD record
ord-65c7acac893047eaa9cdd0b208a1945f
Source dataset
uspto-grants-2012_03
Patent number
US08129377B2

Reaction notes

Loading…