Triethylamine → 6-(3-fluoro-pyridin-4-yl)-3-methyl-2-((3S)-3-(4-morpholin-4-yl-phenyl)-piperazin-1-yl)-3H-pyrimidin-4-one

HRID 1091392Notes

Reaction equation

HRID 1091392 reaction equation
Cl.Cl.Cl.[N:4]1([C:10]2[CH:15]=[CH:14][C:13]([C@H:16]3[NH:21][CH2:20][CH2:19][NH:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.C(N(CC)CC)C.Cl[C:30]1[N:35]([CH3:36])[C:34](=[O:37])[CH:33]=[C:32]([C:38]2[CH:43]=[CH:42][N:41]=[CH:40][C:39]=2[F:44])[N:31]=1>O1CCCC1>[F:44][C:39]1[CH:40]=[N:41][CH:42]=[CH:43][C:38]=1[C:32]1[N:31]=[C:30]([N:18]2[CH2:19][CH2:20][NH:21][C@@H:16]([C:13]3[CH:12]=[CH:11][C:10]([N:4]4[CH2:5][CH2:6][O:7][CH2:8][CH2:9]4)=[CH:15][CH:14]=3)[CH2:17]2)[N:35]([CH3:36])[C:34](=[O:37])[CH:33]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 595768122-Chloro-3-methyl-6-(3-fluoropyridin-4-yl)-3H-pyrimidin-4-oneHCID 66594814(3R)-3-(4-(morpholin-4-yl)phenyl)piperazine trihydrochloride

Product 1

HCID 116048276-(3-fluoro-pyridin-4-yl)-3-methyl-2-((3S)-3-(4-morpholin-4-yl-phenyl)-piperazin-1-yl)-3H-pyrimidin-4-oneYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the above prepared (3R)-3-(4-(morpholin-4-yl)phenyl)piperazine trihydrochloride (0.5 g, 1.40 mmol) and triethylamine (0.8 g, 7.91 mmol) in tetrahydrofuran (10 ml) was added 2-chloro-6-(3-fluoropyridin-4-yl)-3-methyl-(3H)-pyrimidin-4-one (0.3 g, 1.25 mmol) which was prepared by Reference Example 2 portionwise. After stirring 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 column chromatography eluting 5-10% methanol in chloroform to furnish 6-(3-fluoro-pyridin-4-yl)-3-methyl-2-((3S)-3-(4-morpholin-4-yl-phenyl)-piperazin-l-yl)-3H-pyrimidin-4-one (0.41 g, 0.91 mmol, 73%) as white crystals.

Workup

  1. customwas prepared by Reference Example 2 portionwise
  2. customthe resulting suspension was partitioned between chloroform and 1N sodium hydroxide
  3. extractionthe aqueous layer was extracted with chloroform
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting 5-10% methanol in chloroform

Sources & evidence

ORD record
ord-d0f74ba5437046fd8025e124a3e1effa
Source dataset
uspto-grants-2012_03
Patent number
US08129377B2

Reaction notes

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