Hydrochloric Acid → (5-Bromo-2-hydroxyphenyl)[1-(pyridin-2-yl)-1H-pyrazol-4-yl]methanone

HRID 910022Notes

Reaction equation

HRID 910022 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]=[C:6]([CH:12]=O)[C:5]2=[O:14].[NH:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1)[NH2:16].[OH-].[K+].Cl>C(O)(C)C.C(Cl)Cl.O>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([OH:8])=[C:4]([C:5]([C:6]2[CH:12]=[N:16][N:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[CH:7]=2)=[O:14])[CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 786452-HydrazinopyridineHCID 6143096-Bromo-3-formylchromone

Product 1

HCID 57658813(5-Bromo-2-hydroxyphenyl)[1-(pyridin-2-yl)-1H-pyrazol-4-yl]methanoneYield 99.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 6-bromo-3-formylchromone (253 mg) in isopropanol (3 mL) and CH2Cl2 (2 mL) was added 2-hydrazinopyridine (109 mg), and the mixture was stirred for 15 min to form a yellow slurry. The slurry was added KOH (0.25 g) in water (0.25 mL), and the reaction was heated to reflux for 1 h. The reaction mixture was diluted with water, added 3% HCl until pH<1 and extracted with CH2Cl2 (2×). The extract was washed with water and brine, dried (MgSO4) and concentrated to give 342 mg orange foam, which was purified by flash chromatography (SiO2, EA:Hep, 1:1) to give 53 mg (15%) yellow solid: LC/MS (an10p8): Rt 5.0 min, m/z 343.5 [M+H]+; 1H NMR (CDCl3): δ 6.98 (d, J=8.9 Hz, 1H), 7.31 (ddd, J=7.3, 4.9, 0.9 Hz, 1H), 7.60 (dd, J=8.9, 2.5 Hz, 1H), 7.87-7.93 (m, 1H), 8.03 (d, J=2.4 Hz, 1H), 8.04-8.09 (m, 1H), 8.02 (s, 1H), 8.47-8.51 (m, 1H), 9.13 (s, 1H), 11.94 (s, 1H); 13C NMR (CDCl3): δ 110.9, 113.3, 120.8, 121.6, 122.8, 123.1, 130.5, 133.5, 138.9, 139.3, 143.3, 148.7, 161.9, 191.4.

Workup

  1. customto form a yellow slurry
  2. temperaturethe reaction was heated
  3. temperatureto reflux for 1 h
  4. extractionextracted with CH2Cl2 (2×)
  5. washThe extract was washed with water and brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-ef619041dce841dba975dc8ab5c1a9d6
Source dataset
uspto-grants-2011_09
Patent number
US08022063B2

Reaction notes

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