Oxalyl chloride → HCID 66749622, compound

HRID 537054Notes

Reaction equation

HRID 537054 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[O:12][C:13]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:25])=[C:14]([C:16](O)=[O:17])[N:15]=2)[C:8]([CH3:26])=[CH:7][N:6]=1)(=[O:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[CH3:33][O:34][CH:35]([O:38][CH3:39])[CH2:36][NH2:37]>C(Cl)Cl.CN(C=O)C>[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[O:12][C:13]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:25])=[C:14]([C:16]([NH:37][CH2:36][CH:35]([O:38][CH3:39])[O:34][CH3:33])=[O:17])[N:15]=2)[C:8]([CH3:26])=[CH:7][N:6]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 89728Aminoacetaldehyde dimethyl acetalHCID 66749149HCID 66749149, compound

Product 1

HCID 66749622HCID 66749622, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 2-(2-acetamido-5-methylpyridin-4-yl)-5-(2-chlorophenyl)-1,3-oxazole-4-carboxylic acid (0.50 g, 1.34 mmol) in DCM (15 mL) and DMF (0.05 mL) was allowed to stir at 0° C. To this solution was added oxalyl chloride (0.23 mL, 2.69 mmol) dropwise. The reaction mixture was allowed to stir at 0° C. for 15 minutes and then allowed to warm to rt and stir for 2 hr. The reaction mixture was concentrated, and then DCM (15 mL) and TEA (0.38 mL, 2.69 mmol) were added. The reaction mixture was allowed to stir at 0° C. and a solution of 2,2-dimethoxyethanamine (0.29 mL, 2.69 mmol) in DCM (5 mL) was added dropwise. The reaction mixture was allowed to warm to rt and to stir overnight and then concentrated. The residue was redissolved in water and EtOAc. The organic solution was separated and the aqueous solution was further extracted with EtOAc. The organic solutions were combined, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography to give 2-(2-acetamido-5-methylpyridin-4-yl)-5-(2-chlorophenyl)-N-(2,2-dimethoxyethyl)-1,3-oxazole-4-carboxamide (0.226 g, 37%). LCMS (FA): m/z=459 (M+H).

Workup

  1. stirringto stir at 0° C. for 15 minutes
  2. temperatureto warm to rt
  3. stirringstir for 2 hr
  4. concentrationThe reaction mixture was concentrated
  5. stirringto stir at 0° C.
  6. temperatureto warm to rt
  7. stirringto stir overnight
  8. concentrationconcentrated
  9. dissolutionThe residue was redissolved in water
  10. customThe organic solution was separated
  11. extractionthe aqueous solution was further extracted with EtOAc
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-048c02e771a34eef9492b8f41b0fe047
Source dataset
uspto-grants-2014_10
Patent number
US08859768B2

Reaction notes

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