Morpholine → HCID 58133811, compound

HRID 2064314Notes

Reaction equation

HRID 2064314 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H: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]([CH3:36])(=[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]([C@@H: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]([CH3:36])(=[O:34])=[O:35])[CH:4]=1)#[N:2]

Participants

5

Reactant 2

HCID 8083MorpholineHCID 42642248HCID 42642248, compound

Product 1

HCID 58133811HCID 58133811, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

The reaction was carried out under argon. Allyl (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (800 mg, 1.54 mmol; Example 4) and morpholine (1.5 eq., 201 mg, 2.31 mmol) were initially charged in dry THF (25 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., 89 mg, 0.077 mmol) was added, and the reaction mixture was stirred at RT for 90 min (HPLC control). The reaction mixture was then concentrated and the residue was taken up in ethyl acetate (500 ml). The organic phase was washed with saturated ammonium chloride solution (50 ml), with water (50 ml) and with conc. sodium chloride solution (50 ml), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). This gave a colorless amorphous solid (696 mg, purity 86%, 81% of theory).

Workup

  1. customThe reaction mixture was degassed repeatedly (evacuation followed by venting with argon)
  2. concentrationThe reaction mixture was then concentrated
  3. washThe organic phase was washed with saturated ammonium chloride solution (50 ml), with water (50 ml) and with conc. sodium chloride solution (50 ml)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10)
  8. customThis gave a colorless amorphous solid (696 mg, purity 86%, 81% of theory)

Sources & evidence

ORD record
ord-9352c7554702452b911ceccfda05a9a6
Source dataset
uspto-grants-2012_10
Patent number
US08288402B2

Reaction notes

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