Pyridine → HCID 86700686, compound

HRID 1406868Notes

Reaction equation

HRID 1406868 reaction equation
[CH2:1]([O:8][N:9]1[C:15](=[O:16])[N:14]2[CH2:17][C@H:10]1[CH2:11][CH2:12][C@H:13]2[C:18](/[N:20]=[CH:21]\[N:22](C)C)=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1>CCO.CO>[CH2:1]([O:8][N:9]1[C:15](=[O:16])[N:14]2[CH2:17][C@H:10]1[CH2:11][CH2:12][C@H:13]2[C:18]1[O:19][N:22]=[CH:21][N:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 1049PyridineHCID 178484349HCID 178484349, compound

Product 1

HCID 86700686HCID 86700686, compoundYield 4.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

(2S,5R,Z)-6-(benzyloxy)-N-((dimethylamino)methylene)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carboxamide (1.33 g, 4.03 mmol) in EtOH (22 mL) was treated with pyridine (0.64 ml, 8.06 mmol), followed by the addition of a solution of HOSA (547 mg, 4.84 mmol) in MeOH (4.5 mL). The resulting mixture was stirred at rt for 30 minutes and then concentrated under vacuum. The residue was dissolved in DCM/THF (1:2, 30 mL) and washed with water (10 mL). The organic layer was dried overNa2SO4, and concentrated. The residue was re-dissolved in EtOH (22 mL) and 2N HCl (8.0 mL). The mixture was heated at reflux for 20 minutes, concentrated and extracted with DCM (2×). The crude material was purified by prep-HPLC to give (2S,5R)-6-(benzyloxy)-2-(1,2,4-oxadiazol-5-yl)-1,6-diaza-bicyclo[3.2.1]octan-7-one (50 mg, 4.1%) as a light yellow oil. ESI-MS (EI+, 301, m/z): [M+H]+. 1H-NMR (500 MHz, CDCl3): δ 8.44 (s, 1H), 7.45-7.35 (m, 5H), 5.09 (d, J=11.5 Hz, 1H), 4.94 (d, J=11.5 Hz, 1H), 4.85 (d, J=8.0 Hz, 1H), 3.36 (m, 1H), 3.01 (d, J=12.0 Hz, 1H), 2.81 (d, J=12.0 Hz, 1H), 2.37-2.35 (m, 1H), 2.25-2.21 (m, 1H), 2.01-2.00 (m, 1H), 1.85-1.84 (m, 1H).

Workup

  1. concentrationconcentrated under vacuum
  2. dissolutionThe residue was dissolved in DCM/THF (1:2, 30 mL)
  3. washwashed with water (10 mL)
  4. customThe organic layer was dried overNa2SO4, and
  5. concentrationconcentrated
  6. dissolutionThe residue was re-dissolved in EtOH (22 mL)
  7. temperatureThe mixture was heated
  8. temperatureat reflux for 20 minutes
  9. concentrationconcentrated
  10. extractionextracted with DCM (2×)
  11. customThe crude material was purified by prep-HPLC

Sources & evidence

ORD record
ord-bae99e7f53fb47cdae2af1344bc8e6be
Source dataset
uspto-grants-2014_12
Patent number
US08916709B2

Reaction notes

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