Oxalyl chloride → HCID 67370849, compound

HRID 1753142Notes

Reaction equation

HRID 1753142 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:38][CH2:37][CH2:36][N:25]2[C:26](=[O:35])[C:27]2[N:28]([CH:30]=[C:31]([C:33]#[N:34])[CH:32]=2)[CH2:29]3)=[CH:20][CH:19]=1>CN(C=O)C.C(Cl)Cl.N1C=CC=CC=1.O>[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]23[N:38]([C:13]([C:12]4[C:8]([CH3:7])=[N:9][O:10][CH:11]=4)=[O:15])[CH2:37][CH2:36][N:25]2[C:26](=[O:35])[C:27]2[N:28]([CH:30]=[C:31]([C:33]#[N:34])[CH:32]=2)[CH2:29]3)=[CH:20][CH:19]=1

Participants

8

Reactant 3

HCID 65578Oxalyl chlorideHCID 45896923-Methyl-1,2-oxazole-4-carboxylic acidHCID 67367542HCID 67367542, compound

Product 1

HCID 67370849HCID 67370849, compound

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 1049PyridineSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To generate the acid chloride, oxalyl chloride (100 μL, 1.18 mmol) and DMF (1 drop) were added to 3-methyl-1,2-oxazole-4-carboxylic acid (100 mg, 0.84 mmol) in CH2Cl2 (2 mL) at 0° C. The suspension was allowed to stir 15 min at 0° C. followed by 1 hour at room temperature. The resulting solution was concentrated in vacuo (without heating) to give an oil that was dissolved in CH2Cl2 and concentrated in vacuo. To a chilled (0° C.) suspension of the acid chloride (generated as above, 0.84 mmol) in pyridine (0.5 mL) was added a cloudy mixture of 10a-(4-methoxyphenyl)-5-oxo-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazine-7-carbonitrile (50 mg, 0.16 mmol) in pyridine (0.5 mL). The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was then diluted with water (5 mL) and extracted with CH2Cl2 (3×5 mL). The organic fractions were combined, dried (MgSO4) and concentrated in vacuo to give a crude residue that was purified by flash chromatography (Biotage SP4 12 g cartridge, 0 to 5% MeOH in EtOAc) and reverse phase chromatography (5-50s-55-100% acetonitrile-water, water contained 0.1% formic acid). The compound 10a-(4-methoxyphenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-5-oxo-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazine-7-carbonitrile (89) was isolated as a white solid (2.2 mg, yield 3%).

Workup

  1. waitfollowed by 1 hour at room temperature
  2. concentrationThe resulting solution was concentrated in vacuo (without heating)
  3. customto give an oil that
  4. concentrationconcentrated in vacuo
  5. temperatureTo a chilled
  6. additionwas added
  7. temperatureThe reaction mixture was warmed to room temperature
  8. stirringstirred overnight
  9. extractionextracted with CH2Cl2 (3×5 mL)
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customto give a crude residue that
  13. customwas purified by flash chromatography (Biotage SP4 12 g cartridge, 0 to 5% MeOH in EtOAc)

Sources & evidence

ORD record
ord-1ae398c3599e44f3a269102462e92d88
Source dataset
uspto-grants-2015_10
Patent number
US09163029B2

Reaction notes

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