Hydrochloric Acid → HCID 22025340, compound

Temperature

0 °C

N-(3-Chloro-2-methoxy-5,6-dimethyl-phenyl)-acetamide (3.36 g, 17.4 mmol) is dissolved in HOAc (75 mL) and conc. HCl (30 mL) in a 1 L round bottom flask. The reaction is cooled to 0° C. with an ice/salt bath. Although some starting material crystallizes, a solution of NaNO2 (5.9 g, 86 mmol) in water (25 mL) is added portion-wise over 5 min. All material goes into solution and the reacion is stoppered and stirred 45 min. HPLC shows very little sm. Ice cold water (800 mL) is was added slowly and the reaction was stirred 1 h. A precipitate forms. The solid is filtered and washed with ice cold water (500 mL). The material is dried with suction and then pumped to a constant weight 3.3 g. The solid is partially dissolved in toluene (35 mL) and stirred under N2. After stirring 18 h, the reaction is heated for 4 hours and cooled. The reaction is diluted with EtOAc and washed with NaHCO3, brine, dried (MgSO4) and concentrated. The crude product is purified by column chromatography (silica, 30% EtOAc/hexanes) to provide the desired product, 6-chloro-7-methoxy-4-methyl-1H-indazole.

1. customAlthough some starting material crystallizes
2. stirringthe reaction was stirred 1 h
3. filtrationThe solid is filtered
4. washwashed with ice cold water (500 mL)
5. customThe material is dried with suction
6. dissolutionThe solid is partially dissolved in toluene (35 mL)
7. stirringstirred under N2
8. stirringAfter stirring 18 h
9. temperaturethe reaction is heated for 4 hours
10. temperaturecooled
11. additionThe reaction is diluted with EtOAc
12. washwashed with NaHCO3, brine
13. dry with materialdried (MgSO4)
14. concentrationconcentrated
15. customThe crude product is purified by column chromatography (silica, 30% EtOAc/hexanes)

ORD record

ord-cc3d07a142de43c993bd55af94fd01c6

Source dataset

uspto-grants-2006_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07078425B2