Pyridine → HCID 67452021, compound

HRID 869200Notes

Reaction equation

HRID 869200 reaction equation
[F:1][C:2]1[C:3]([C:8]2([CH2:12][N:13]([C:21]3[N:22]=[N:23][C:24]([CH:27]=O)=[CH:25][CH:26]=3)[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:11][CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.Cl.[NH2:30][OH:31].C([O-])(=O)C.[Na+].N1C=CC=CC=1.C1C(=O)N(Cl)C(=O)C1.[C:51]([O:55][CH3:56])(=[O:54])[C:52]#[CH:53]>C(O)C.O>[CH3:56][O:55][C:51]([C:52]1[O:31][N:30]=[C:27]([C:24]2[N:23]=[N:22][C:21]([N:13]([C:14]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:20])[CH2:12][C:8]3([C:3]4[C:2]([F:1])=[CH:7][CH:6]=[CH:5][N:4]=4)[CH2:9][CH2:10][CH2:11]3)=[CH:26][CH:25]=2)[CH:53]=1)=[O:54]

Participants

9

Reactant 6

HCID 1049PyridineHCID 13536Methyl propiolateHCID 31398ChlorosuccinimideHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 86686145HCID 86686145, compound

Product 1

HCID 67452021HCID 67452021, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
24 °C

Procedure

To t-butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-formylpyridazin-3-yl)carbamate (1.4 g, 3.6 mmol) in ethanol (10 mL) and water (2 mL) was added hydroxylamine hydrochloride (0.27 g, 3.8 mmol) followed by sodium acetate (0.32 g, 3.8 mmol) and stirred at 24° C. for 30 min. The crude reaction mixture was concentrated and diluted with EtOAc. The organic layer was washed with satd. aq. NaHCO3 and brine, then dried over sodium sulfate, filtered, and concentrated. The crude mixture was then diluted in THF (2 mL) and pyridine (57 mg, 0.72 mmol) then treated with NCS (0.58 g, 4.35 mmol) and heated to 40° C. for 1.5 h. The crude mixture was then treated with methyl propiolate (0.30 g, 3.56 mmol) and TEA (0.36, 3.56 mmol), and the reaction was stirred for 45 min. The reaction mixture was concentrated and diluted with EtOAc, and then washed with satd. aq. NaHCO3 and brine. The organic layer was dried over sodium sulfate, filtered, concentrated, and purified by reverse phase chromatography to give a white solid (0.53 g, 31%).

Workup

  1. customThe crude reaction mixture
  2. concentrationwas concentrated
  3. additiondiluted with EtOAc
  4. washThe organic layer was washed with satd
  5. dry with materialaq. NaHCO3 and brine, then dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additionThe crude mixture was then diluted in THF (2 mL)
  9. temperatureheated to 40° C. for 1.5 h
  10. stirringthe reaction was stirred for 45 min
  11. concentrationThe reaction mixture was concentrated
  12. additiondiluted with EtOAc
  13. washwashed with satd
  14. dry with materialThe organic layer was dried over sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated
  17. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-ac45c2a3d19b43919c1f7fe1e2a7a7dd
Source dataset
uspto-grants-2015_03
Patent number
US08969346B2

Reaction notes

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