Acetic Acid → HCID 86637190, compound

HRID 1854498Notes

Reaction equation

HRID 1854498 reaction equation
[Cl:1][C:2]1[C:3]([C:11]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)=O)=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:19][NH:20][NH2:21].CC(O)=O>C(O)CCC>[Cl:1][C:2]1[C:3]([C:11]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)=[N:21][NH:20][CH3:19])=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 176Acetic Acid2×HCID 6061Methylhydrazine2×HCID 58010041HCID 58010041, compound

Product 1

HCID 86637190HCID 86637190, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of (5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)(cyclohexyl)methanone (0.383 g, 1.46 mmol; Example #23, Step B), methylhydrazine (0.24 mL, 4.56 mmol), and AcOH (0.084 mL, 1.47 mmol) in n-butanol (10 mL) was heated at about 135° C. for about 18 h. During this time, water was distilled from the reaction mixture via the use of a Dean-Stark trap. Additional methylhydrazine (0.24 mL, 4.6 mmol) and AcOH (0.084 mL, 1.5 mmol) were added and the reaction mixture was heated at reflux for about 2 days. The reaction was cooled to ambient temperature and concentrated under reduced pressure. The crude product was diluted with EtOAc (50 mL), washed with saturated aqueous NaHCO3 (30 mL) and brine (30 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (0-35% EtOAc in heptane gradient as the eluent to provide 5-chloro-4-(cyclohexyl(2-methylhydrazono)methyl)-1H-pyrrolo[2,3-b]pyridine (0.261 g, 62%): LC/MS (Table 2, Method d) Rt=2.53 min; m/z: 291 and 293 (M+H)+.

Workup

  1. distillationDuring this time, water was distilled from the reaction mixture via the use of a Dean-Stark trap
  2. temperaturethe reaction mixture was heated
  3. temperatureat reflux for about 2 days
  4. temperatureThe reaction was cooled to ambient temperature
  5. concentrationconcentrated under reduced pressure
  6. additionThe crude product was diluted with EtOAc (50 mL)
  7. washwashed with saturated aqueous NaHCO3 (30 mL) and brine (30 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified by silica gel chromatography (0-35% EtOAc in heptane gradient as the eluent

Sources & evidence

ORD record
ord-13000f7f4f554e8abb20462f4e5bc734
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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