Ammonia → Methyl (6S)-8-ethyl-10-(methoxy)-6-methyl-1,9-dioxo-1,2,6,7,8,9-hexahydropyrido-[3',4':4,5]pyrrolo[1,2-a]-pyrazine-4-carboxylate

HRID 2114857Notes

Reaction equation

HRID 2114857 reaction equation
[CH2:1]([N:3]1[CH2:8][C@H:7]([CH3:9])[N:6]2[C:10]([C:20]([C:22]([O:24][CH3:25])=[O:23])=[CH2:21])=[C:11]([C:15]([O:17]CC)=O)[C:12]([O:13][CH3:14])=[C:5]2[C:4]1=[O:26])[CH3:2].[NH3:27]>C1(C)C=CC=CC=1.CO.C(Cl)(Cl)Cl.[O-2].[Mn+4].[O-2]>[CH2:1]([N:3]1[CH2:8][C@H:7]([CH3:9])[N:6]2[C:10]3[C:20]([C:22]([O:24][CH3:25])=[O:23])=[CH:21][NH:27][C:15](=[O:17])[C:11]=3[C:12]([O:13][CH3:14])=[C:5]2[C:4]1=[O:26])[CH3:2]

Participants

7

Reactant 2

HCID 222AmmoniaHCID 86612121Ethyl (4S)-2-ethyl-8-(methoxy)-6-[1-(methoxycarbonyl)vinyl]-4-methyl-1-oxo-1,2,3,4-tetrahydro-pyrrolo[1,2-a]-pyrazine-7-carboxylate

Product 1

HCID 86612123Methyl (6S)-8-ethyl-10-(methoxy)-6-methyl-1,9-dioxo-1,2,6,7,8,9-hexahydropyrido-[3',4':4,5]pyrrolo[1,2-a]-pyrazine-4-carboxylate

Reagents, catalysts & solvents 4

HCID 178418406HCID 178418406, compoundCatalystHCID 887MethanolSolvent2×HCID 1140TolueneSolvent2×HCID 6212ChloroformSolvent

Procedure

A solution of ethyl (4S)-2-ethyl-8-(methoxy)-6-[1-(methoxycarbonyl)vinyl]-4-methyl-1-oxo-1,2,3,4-tetrahydro-pyrrolo[1,2-a]-pyrazine-7-carboxylate (0.19 g, 0.54 mmol) in a mixture of toluene (10 mL) and methanol (4 mL) was treated with a saturated solution of ammonia in methanol (10 mL). The mixture was stirred at rt overnight. The product mixture concentrated under vacuum to provide the corresponding cyclization product. Treatment of the above intermediate (0.34 g, 1.01 mmol) and manganese(IV) oxide (0.26 g, 3.04 mmol) in toluene (10 mL) was heated in a sealed tube in an oil bath 80° C. overnight. The reaction mixture was cooled to rt, diluted with chloroform (100 mL) and filtered through a pad of Celite. The filtrate was concentrated under vacuum. The filtrate was subjected to column chromatography on silica gel eluting with ethyl acetate. Collection and concentration of appropriate fractions provided the titled compound.

Workup

  1. concentrationThe product mixture concentrated under vacuum
  2. customto provide the corresponding cyclization product
  3. temperatureThe reaction mixture was cooled to rt
  4. filtrationfiltered through a pad of Celite
  5. concentrationThe filtrate was concentrated under vacuum
  6. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-b24792c186b747be8d3aa2912c73809d
Source dataset
uspto-grants-2008_10
Patent number
US07435735B2

Reaction notes

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