Acetic Anhydride → 5-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid [1-cyclopropyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide

HRID 1480141Notes

Reaction equation

HRID 1480141 reaction equation
[CH:1]1([C:4]([NH:10][C:11]([C:13]2[CH:18]=[C:17]([O:19][CH2:20][C:21]([F:24])([F:23])[F:22])[C:16]([Br:25])=[CH:15][N:14]=2)=[O:12])([C:6](=[NH:9])[NH:7][OH:8])[CH3:5])[CH2:3][CH2:2]1.[CH2:26](N(CC)CC)[CH3:27].C(OC(=O)C)(=O)C>CN(C=O)C>[CH:1]1([C:4]([NH:10][C:11]([C:13]2[CH:18]=[C:17]([O:19][CH2:20][C:21]([F:24])([F:22])[F:23])[C:16]([Br:25])=[CH:15][N:14]=2)=[O:12])([C:6]2[N:9]=[C:26]([CH3:27])[O:8][N:7]=2)[CH3:5])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 178464905HCID 178464905, compound

Product 1

HCID 902039835-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid [1-cyclopropyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amideYield 58.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid [1-cyclopropyl-1-(N-hydroxycarbamimidoyl)-ethyl]-amide (Example 78f, 800 mg, 1.88 mmol) in dry DMF (10 ml) was added triethylamine (190 mg, 262 μl, 1.88 mmol) followed by addition of acetic anhydride (192 mg, 1.88 mmol). The reaction mixture was stirred at room temperature for 1 hours and was then stirred at 125° C. for 30 min under microwave radiation. DMF was removed in vacuo and the residue was dissolved in ethylacetate which was extracted with an 1.0M aqueous solution of sodium bicarbonate. The organic phase was dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/ethylacetate gradient to yield the title compound (492 mg, 47%) as a light yellow oil. MS (ESI, m/z): 449.3 (M+H+).

Workup

  1. stirringwas then stirred at 125° C. for 30 min under microwave radiation
  2. customDMF was removed in vacuo
  3. dissolutionthe residue was dissolved in ethylacetate which
  4. extractionwas extracted with an 1.0M aqueous solution of sodium bicarbonate
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. customevaporated down to dryness
  7. customThe crude material was purified by flash chromatography on silica eluting with a heptane/ethylacetate gradient

Sources & evidence

ORD record
ord-1f56f3d0f9c445b09e67a649a856ee01
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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