Oxalyl chloride → 10a-(4-methoxyphenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-7-nitro-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one

HRID 1910954Notes

Reaction equation

HRID 1910954 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][C:8]1[C:12]([C:13]([OH:15])=O)=[CH:11][O:10][N:9]=1.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]23[NH:39][CH2:38][CH2:37][N:25]2[C:26](=[O:36])[C:27]2[N:28]([CH:30]=[C:31]([N+:33]([O-:35])=[O:34])[CH:32]=2)[CH2:29]3)=[CH:20][CH:19]=1>CN(C=O)C.C(Cl)Cl.N1C=CC=CC=1>[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]23[N:39]([C:13]([C:12]4[C:8]([CH3:7])=[N:9][O:10][CH:11]=4)=[O:15])[CH2:38][CH2:37][N:25]2[C:26](=[O:36])[C:27]2[N:28]([CH:30]=[C:31]([N+:33]([O-:35])=[O:34])[CH:32]=2)[CH2:29]3)=[CH:20][CH:19]=1

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 45896923-Methyl-1,2-oxazole-4-carboxylic acidHCID 6737065010a-(4-methoxyphenyl)-7-nitro-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one

Product 1

HCID 5337344110a-(4-methoxyphenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-7-nitro-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-oneYield 68%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To generate the acid chloride, oxalyl chloride (600 μL, 7.0 mmol) and DMF (1 drop) were added to 3-methyl-1,2-oxazole-4-carboxylic acid (441 mg, 3.47 mmol) in CH2Cl2 (6 mL) at 0° C. The suspension was allowed to stir 15 minutes at 0° C. followed by 1 hour at room temperature. The resulting solution was concentrated in vacuo (without heating) to give a oil that was further dried under nitrogen. To a chilled suspension of the acid chloride (generated as above, 3.47 mmol) in pyridine (3 mL) was added 10a-(4-methoxyphenyl)-7-nitro-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (190 mg, 0.58 mmol) in pyridine (4 mL). The reaction mixture was stirred at 0° C. to room temperature for 45 minutes and was then quenched with water (15 mL) and extracted with CH2Cl2 (4×15 mL). The organic fractions were washed with brine, dried (MgSO4), filtrated and concentrated to yield a residue that was purified by triturating with acetone to give 10a-(4-methoxyphenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-7-nitro-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (124) (170 mg, yield 68%).

Workup

  1. waitfollowed by 1 hour at room temperature
  2. concentrationThe resulting solution was concentrated in vacuo (without heating)
  3. customto give a oil that
  4. customwas further dried under nitrogen
  5. stirringThe reaction mixture was stirred at 0° C. to room temperature for 45 minutes
  6. customwas then quenched with water (15 mL)
  7. extractionextracted with CH2Cl2 (4×15 mL)
  8. washThe organic fractions were washed with brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltrated
  11. concentrationconcentrated
  12. customto yield a residue that
  13. customwas purified
  14. customby triturating with acetone

Sources & evidence

ORD record
ord-e12f011cb2744880babed720299a58e8
Source dataset
uspto-grants-2013_12
Patent number
US08604034B2

Reaction notes

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