Morpholine → 2-(Methylsulfonyl)-4-(5-(morpholinosulfonyl)thiophen-2-yl)pyrimidine

HRID 507550Notes

Reaction equation

HRID 507550 reaction equation
CS[C:3]1[N:8]=[C:7]([C:9]2[S:13][C:12]([S:14](Cl)(=[O:16])=[O:15])=[CH:11][CH:10]=2)[CH:6]=[CH:5][N:4]=1.[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.[CH2:24](N(CC)CC)C.OO[S:33]([O-:35])=[O:34].[K+]>O1CCCC1.CC(C)=O.O.O>[CH3:24][S:33]([C:3]1[N:8]=[C:7]([C:9]2[S:13][C:12]([S:14]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)(=[O:16])=[O:15])=[CH:11][CH:10]=2)[CH:6]=[CH:5][N:4]=1)(=[O:35])=[O:34]

Participants

8

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 27369955-(2-(Methylthio)-4-pyrimidinyl)-2-thiophenesulfonyl chlorideHCID 23707502Potassium hydroxy sulfite

Product 1

HCID 602043782-(Methylsulfonyl)-4-(5-(morpholinosulfonyl)thiophen-2-yl)pyrimidineYield 73.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 18366337Propan-2-one--water (1/1)Solvent

Procedure

A mixture of 5-(2-(methylthio)pyrimidin-4-yl)thiophene-2-sulfonyl chloride (200 mg, 0.65 mmol), morpholine (62 mg, 0.72 mmol) and triethylamine (78 mg, 0.78 mmol) in tetrahydrofuran (5 mL) was stirred at rt for 2 days. Water (50 mL) was added and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate and filtered. The solvent was evaporated in vacuo and the residue was washed with diethyl ether (2 mL) to give a white solid. The solid was dissolved in 30 mL of acetone-water (1:1) and then oxone (2 g) was added. After stirring at rt for 20 h the mixture was concentrated in vacuo to remove the acetone. The white precipitate was filtered off, washed with water and dried to afford the title compound (186 mg, 73%). MS (M+H)+ 390.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
  2. washThe combined organic layer was washed with brine (50 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customThe solvent was evaporated in vacuo
  6. washthe residue was washed with diethyl ether (2 mL)
  7. customto give a white solid
  8. stirringAfter stirring at rt for 20 h the mixture
  9. concentrationwas concentrated in vacuo
  10. customto remove the acetone
  11. filtrationThe white precipitate was filtered off
  12. washwashed with water
  13. customdried

Sources & evidence

ORD record
ord-8690195d7efc4f38b511169274fd3a82
Source dataset
uspto-grants-2010_08
Patent number
US07786132B2

Reaction notes

Loading…