3-Methoxybenzoic Acid → N-{3-(3-Fluoro-phenyl)-6-methoxy-1H-indazol-5-ylmethyl}-3-methoxy-benzamide

HRID 1610163Notes

Reaction equation

HRID 1610163 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH3:20])=[C:14]([CH2:17][NH2:18])[CH:15]=3)[NH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH3:40][O:41][C:42]1[CH:43]=[C:44]([CH:48]=[CH:49][CH:50]=1)[C:45](O)=[O:46].Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH3:20])=[C:14]([CH2:17][NH:18][C:45](=[O:46])[C:44]4[CH:48]=[CH:49][CH:50]=[C:42]([O:41][CH3:40])[CH:43]=4)[CH:15]=3)[NH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 114613-Methoxybenzoic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22260835C-{3-(3-Fluoro-phenyl)-6-methoxy-1H-indazol-5-yl}-methylamine

Product 1

HCID 22260695N-{3-(3-Fluoro-phenyl)-6-methoxy-1H-indazol-5-ylmethyl}-3-methoxy-benzamideYield 24.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A total of 25.6 mg of C-{3-(3-fluoro-phenyl)-6-methoxy-1H-indazol-5-yl}-methylamine obtained in Production Example II-26 was dissolved in 1.9 ml of dimethylformamide, 15.3 mg of 1-hydroxybenzotriazole, 0.066 ml of diisopropylethylamine and 14.4 mg of 3-methoxybenzoic acid were added thereto, and 27.2 mg of 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (i.e., WSC.HCl) was added thereto under ice-cooling and stirring. After stirring at room temperature for 5 hours, water was added and the mixture was extracted with ethyl acetate. The resulting organic layer was washed with 0.5 N aqueous sodium hydroxide solution, 1 N hydrochloric acid and saturated brine, dried over magnesium sulfate, and the solvent was evaporated. The residue was purified and separated by silica gel column chromatography (dichloromethane:methanol=10:1), to give 9.24 mg of the title compound as pale yellow crystals.

Workup

  1. temperatureunder ice-cooling
  2. stirringAfter stirring at room temperature for 5 hours
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe resulting organic layer was washed with 0.5 N aqueous sodium hydroxide solution, 1 N hydrochloric acid and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. customthe solvent was evaporated
  7. customThe residue was purified
  8. customseparated by silica gel column chromatography (dichloromethane:methanol=10:1)

Sources & evidence

ORD record
ord-5a81992e068443ac90d18d84e15bc1dc
Source dataset
uspto-grants-2006_01
Patent number
US06982274B2

Reaction notes

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