Morpholine → HCID 58133834, compound

HRID 336913Notes

Reaction equation

HRID 336913 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])[N:10]2[S:33]([CH3:36])(=[O:35])=[O:34])=[C:5]([S:37]([CH3:40])(=[O:39])=[O:38])[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])[N:10]2[S:33]([CH3:36])(=[O:34])=[O:35])=[C:5]([S:37]([CH3:40])(=[O:38])=[O:39])[CH:4]=1)#[N:2]

Participants

5

Reactant 2

HCID 8083MorpholineHCID 58133676HCID 58133676, compound

Product 1

HCID 58133834HCID 58133834, compoundYield 70%

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-3-(methylsulfonyl)-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (288 mg, 0.482 mmol) and morpholine (1.5 eq., 63 mg, 0.723 mmol) were initially charged in dry THF (5 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., 28 mg, 0.024 mmol) was added, and the reaction mixture was stirred at RT for 1.5 h (HPLC control). The mixture was then concentrated under reduced pressure, and the residue was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→75:25). This gave the title compound as a solid (187 mg, 70% of theory).

Workup

  1. customThe reaction mixture was degassed repeatedly (evacuation followed by venting with argon)
  2. concentrationThe mixture was then concentrated under reduced pressure
  3. customthe residue was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→75:25)

Sources & evidence

ORD record
ord-5a1bbf556bb74c88b933b6c6ffe385b2
Source dataset
uspto-grants-2014_11
Patent number
US08889700B2

Reaction notes

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