Morpholine → HCID 25260709, compound

HRID 1894353Notes

Reaction equation

HRID 1894353 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([CH3:41])[C@:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([CH3:13])[N:11]([C:21]([N:23]3[CH2:28][CH2:27][NH:26][C:25](=[O:29])[CH2:24]3)=[O:22])[C:10]([C:30]3[C:31]([O:38][CH2:39][CH3:40])=[N:32][C:33](SC)=[N:34][CH:35]=3)=[N:9]2)=[CH:4][CH:3]=1.ClC1C=C(C=CC=1)C(OO)=O.S(=O)(O)[O-].[Na+].[NH:58]1[CH2:63][CH2:62][O:61][CH2:60][CH2:59]1>C(Cl)Cl.O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([CH3:41])[C@:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([CH3:13])[N:11]([C:21]([N:23]3[CH2:28][CH2:27][NH:26][C:25](=[O:29])[CH2:24]3)=[O:22])[C:10]([C:30]3[C:31]([O:38][CH2:39][CH3:40])=[N:32][C:33]([N:58]4[CH2:63][CH2:62][O:61][CH2:60][CH2:59]4)=[N:34][CH:35]=3)=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 70297m-Chloroperbenzoic acidHCID 23665763Sodium BisulfiteHCID 25260708HCID 25260708, compound

Product 1

HCID 25260709HCID 25260709, compoundYield 55.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of rac-4-[(4S*,5R*)-4,5-bis-(4-chloro-phenyl)-2-(4-ethoxy-2-methylsulfanyl-pyrimidin-5-yl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-2-one (160 mg, 0.261 mmol) in methylene chloride cooled to 0° C. was added 100 mg of m-chloroperoxybenzoic acid (≦77%, Aldrich). After 10 min, sodium bisulfite solution was added to quench the reaction. The product was extracted with methylene chloride. The organic layer was washed with saturated solution of sodium bicarbonate, brine, dried over Na2SO4 and concentrated to give the crude sulphoxide as light yellow foam. The crude sulphoxide/sulphone was taken in 20 mL of tetrahydrofuran, and morpholine (200 uL, 3.34 mmol, Aldrich) was added. The mixture was heated at reflux overnight. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure. Purification of the crude residue by flash column chromatography (silica gel, eluting with 50-100% ethyl acetate in hexanes, then with 0-5% methanol in ethyl acetate) gave the tittle compound (94 mg, 55%). HR-MS (ES, m/z) calculated for C32H36N7O4Cl2 [(M+H)+] 652.2201, observed 652.2202.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionThe product was extracted with methylene chloride
  4. washThe organic layer was washed with saturated solution of sodium bicarbonate, brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto give the crude sulphoxide as light yellow foam
  8. temperatureThe mixture was heated
  9. temperatureat reflux overnight
  10. concentrationthe reaction mixture was concentrated under reduced pressure
  11. customPurification of the crude residue by flash column chromatography (silica gel
  12. washeluting with 50-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-b99cfc7528094cf1811bf2de84d047e2
Source dataset
uspto-grants-2013_08
Patent number
US08513239B2

Reaction notes

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