4-Methylmorpholine → 6-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-4-oxo-hexahydro-pyrrolo[1,2-a]pyrazine-2-carboxylic acid methyl ester

HRID 2038989Notes

Reaction equation

HRID 2038989 reaction equation
[CH3:1][O:2][C:3]([N:5]1[CH2:10][C:9](=[O:11])[N:8]2[CH:12]([C:15]([OH:17])=O)[CH2:13][CH2:14][CH:7]2[CH2:6]1)=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.Cl.[NH2:50][CH2:51][C:52]([C:54]1[CH:59]=[CH:58][C:57]([Br:60])=[CH:56][CH:55]=1)=[O:53]>CN(C)C=O>[CH3:1][O:2][C:3]([N:5]1[CH2:10][C:9](=[O:11])[N:8]2[CH:12]([C:15](=[O:17])[NH:50][CH2:51][C:52]([C:54]3[CH:59]=[CH:58][C:57]([Br:60])=[CH:56][CH:55]=3)=[O:53])[CH2:13][CH2:14][CH:7]2[CH2:6]1)=[O:4]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 27982162-Amino-1-(4-bromophenyl)ethan-1-one hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666208694-Oxo-hexahydro-pyrrolo[1,2-a]pyrazine-2,6-dicarboxylic acid 2-methyl ester

Product 1

HCID 666208976-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-4-oxo-hexahydro-pyrrolo[1,2-a]pyrazine-2-carboxylic acid methyl esterYield 75.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-oxo-hexahydro-pyrrolo[1,2-a]pyrazine-2,6-dicarboxylic acid 2-methyl ester (81 mg, 0.33 mmol), HATU (152 mg, 0.40 mmol), and 4-methyl morpholine (146 μL, 1.33 mmol) in dimethylformamide (4 mL) was stirred at ambient temperature for 5 minutes. 2-Amino-1-(4-bromo-phenyl)-ethanone hydrochloride (91 mg, 0.37 mmol) was added to the reaction mixture. After 1 hour the solvent was removed under reduced pressure and the resulting residue was taken up in ethyl acetate (10 mL). The resulting mixture contained a solid and was filtered. The solvent was removed under reduced pressure from the filtrate. The resulting residue was subjected to flash chromatography with eluent of (10% methanol in ethyl acetate) and hexane. The product-containing fractions were combined and the solvent was removed under reduced pressure to provide 6-[2-(4-bromo-phenyl)-2-oxo-ethylcarbamoyl]-4-oxo-hexahydro-pyrrolo[1,2-a]pyrazine-2-carboxylic acid methyl ester (110 mg, 0.25 mmol, 75%). C18H20BrN3O5 calculated 437.1 observed [M+1]+ 438.1; rt=1.82 min.

Workup

  1. customAfter 1 hour the solvent was removed under reduced pressure
  2. filtrationwas filtered
  3. customThe solvent was removed under reduced pressure from the filtrate
  4. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-a9d5a9dda8124273a7ce48777e15920c
Source dataset
uspto-grants-2013_11
Patent number
US08575118B2

Reaction notes

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