Acetic Acid → HCID 136342280, compound

HRID 1854496Notes

Reaction equation

HRID 1854496 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.Cl.[NH2:20][OH:21].C(N(CC)C(C)C)(C)C.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:20][OH:21])=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic Acid3×HCID 81531Diisopropylethylamine3×HCID 443297Hydroxyamine hydrochloride3×HCID 58010041HCID 58010041, compound

Product 1

HCID 136342280HCID 136342280, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)(cyclohexyl)methanone (0.35 g, 1.33 mmol; Example #23, Step B), hydroxylamine hydrochloride (0.46 g, 6.7 mmol), N,N-diisopropylethylamine (1.6 mL, 9.32 mmol) and AcOH (0.2 mL, 3.5 mmol) in n-butanol (20 mL) was heated at about 120° C. for about 18 h. Additional hydroxylamine hydrochloride (0.185 g, 2.66 mmol), N,N-diisopropylethylamine (0.70 mL, 4.0 mmol), and AcOH (0.15 mL, 2.7 mmol) were added to the mixture and the reaction was heated at about 120° C. for about 18 h. Additional amounts of hydroxylamine hydrochloride (0.185 g, 2.66 mmol), DIEA (0.70 mL, 4.0 mmol), and AcOH (0.15 mL, 2.7 mmol) were added to the mixture and the reaction was heated at about 130° C. for about 3 days. The reaction was cooled to ambient temperature and concentrated under reduced pressure. The residue was diluted with EtOAc (50 mL) and washed with saturated aqueous NaHCO3 (3×40 mL) and brine (20 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (0-70% EtOAc in heptane gradient as the eluent to provide (5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)(cyclohexyl)methanone oxime as an off white solid (0.193 g, 52%): LC/MS (Table 2, Method a) Rt=2.22 min; m/z: 276 and 278 (M−H)−.

Workup

  1. temperaturethe reaction was heated at about 120° C. for about 18 h
  2. temperaturethe reaction was heated at about 130° C. for about 3 days
  3. temperatureThe reaction was cooled to ambient temperature
  4. concentrationconcentrated under reduced pressure
  5. additionThe residue was diluted with EtOAc (50 mL)
  6. washwashed with saturated aqueous NaHCO3 (3×40 mL) and brine (20 mL)
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by silica gel chromatography (0-70% EtOAc in heptane gradient as the eluent

Sources & evidence

ORD record
ord-c1fa483fc0dd48dbb5166210eb4dea65
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

Loading…