Hydrochloric Acid → 5-Amino-3-(phenylethynyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}indazole

HRID 25446Notes

Reaction equation

HRID 25446 reaction equation
O.Cl.[N+:3]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[N:10]=[C:9]2[C:23]#[C:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([O-])=O>C(O)C.[Fe]>[NH2:3][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:20])[CH3:21])[N:10]=[C:9]2[C:23]#[C:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 686721405-nitro-3-phenylethynyl-1-(2-trimethylsilanylethoxymethyl)-1H-indazole

Product 1

HCID 686734445-Amino-3-(phenylethynyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}indazoleYield 14.2%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
20 °C

Procedure

5-Amino-3-phenylethynyl-1-(2-trimethylsilanylethoxymethyl)-1H-indazole can be obtained in the following way: 18 ml of water, 0.2 ml of an aqueous 12N hydrochloric acid solution and 0.36 g of powdered iron are added to a solution of 0.84 g of 5-nitro-3-phenylethynyl-1-(2-trimethylsilanylethoxymethyl)-1H-indazole in 15 ml of absolute ethanol, at the reflux temperature of the solvent. The reaction mixture is then stirred at the reflux of the solvent for 4 hours, and is then cooled to a temperature in the region of 20° C. After filtration through Celite® and washing with absolute ethanol, the filtrate is concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 35° C. The residue thus obtained is purified by chromatography under argon pressure (50 kPa), on a column of 60 g of silica (particle size 40-63 μm), eluting successively with cyclohexane/ethyl acetate (95/5; 90/10; 80/20; 70/30; 60/40; 50/50; 30/70 by volume) mixtures, and then with pure ethyl acetate and, finally, with pure ethanol. The fractions containing the expected product are pooled and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 35° C. 0.11 g of 5-amino-3-phenylethynyl-1-(2-trimethylsilanylethoxymethyl)-1H-indazole is thus obtained in the form of a brown oil (Rf=0.47, silica gel thin layer chromatography, eluent: cyclohexane/ethyl acetate (60/40 by volume)). 0.2 g of 5-amino-3-phenylethynyl-1H-indazole is also obtained in the form of a brown oil (Rf=0.17, silica gel thin layer chromatography, eluent: cyclohexane/ethyl acetate (60/40 by volume)).

Workup

  1. temperaturereflux of the solvent for 4 hours
  2. filtrationAfter filtration through Celite®
  3. washwashing with absolute ethanol
  4. concentrationthe filtrate is concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 35° C
  5. customThe residue thus obtained
  6. customis purified by chromatography under argon pressure (50 kPa)
  7. washon a column of 60 g of silica (particle size 40-63 μm), eluting successively with cyclohexane/ethyl acetate (95/5; 90/10; 80/20; 70/30; 60/40; 50/50; 30/70 by volume) mixtures
  8. additionThe fractions containing the expected product
  9. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 35° C

Sources & evidence

ORD record
ord-97980aa15c2a4c0183e954e79a365d72
Source dataset
uspto-grants-2005_02
Patent number
US06858638B2

Reaction notes

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