Morpholine → HCID 58133740, compound

HRID 336905Notes

Reaction equation

HRID 336905 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]([C:15]([O:17]CC=C)=[O:16])=[C:13]([CH3:21])[N:12]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=3)[C:11](=[O:32])[NH:10]2)=[C:5]([S:33]([CH2:36][CH2:37][OH:38])(=[O:35])=[O:34])[CH:4]=1)#[N:2].N1CCOCC1>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]([C:15]([OH:17])=[O:16])=[C:13]([CH3:21])[N:12]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:30])([F:31])[F:29])[CH:23]=3)[C:11](=[O:32])[NH:10]2)=[C:5]([S:33]([CH2:36][CH2:37][OH:38])(=[O:35])=[O:34])[CH:4]=1)#[N:2]

Participants

5

Reactant 2

HCID 8083MorpholineHCID 58133696HCID 58133696, compound

Product 1

HCID 58133740HCID 58133740, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

The reaction was carried out under argon. Allyl (rac)-4-[4-cyano-2-((2-hydroxyethyl)sulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (150 mg, 0.273 mmol) and morpholine (1.5 eq., 35.6 mg, 0.409 mmol) were initially charged in dry THF (4 ml) at RT. The reaction mixture was degassed repeatedly (evacuation followed by venting with argon). Under protective gas, tetrakis(triphenylphosphine)palladium(0) (0.05 eq., 15.8 mg, 0.014 mmol) was added, and the reaction mixture was stirred at RT for 1 h (HPLC control). The mixture was then concentrated, and the residue was taken up in ethyl acetate (60 ml). The organic phase was washed repeatedly with saturated ammonium chloride solution (3×20 ml), water (20 ml) and saturated sodium chloride solution (20 ml), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→80:20). The title compound was obtained as a solid (60 mg, 43% of theory).

Workup

  1. customThe reaction mixture was degassed repeatedly (evacuation followed by venting with argon)
  2. concentrationThe mixture was then concentrated
  3. washThe organic phase was washed repeatedly with saturated ammonium chloride solution (3×20 ml), water (20 ml) and saturated sodium chloride solution (20 ml)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→80:20)

Sources & evidence

ORD record
ord-b5b3abbd667a47d7af656a5172327949
Source dataset
uspto-grants-2014_11
Patent number
US08889700B2

Reaction notes

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