1H-Benzotriazole-1-methanol → 5-(2-(Methylamino)pyridin-4-yloxy)indole-1-carboxylic acid methylamide

HRID 2376899Notes

Reaction equation

HRID 2376899 reaction equation
[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH2:21])[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4].N1(CO)C2C=CC=C[C:25]=2N=N1.[BH4-].[Na+]>C(O)C.CN(C)C=O>[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:21][CH3:25])[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4]

Participants

6

Reactant 3

HCID 2241691H-Benzotriazole-1-methanolHCID 4311764Sodium borohydrideHCID 21949141N1-Methyl-5-(2-amino-4-pyridyl)oxy-1H-1-indolecarboxamide

Product 1

HCID 210548865-(2-(Methylamino)pyridin-4-yloxy)indole-1-carboxylic acid methylamideYield 20.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

N1-Methyl-5-(2-aminopyridin-4-yl)oxy-1H-1-indolecarboxamide (5.00 g, 17.7 mmol, Production example 5-1) was dissolved in ethanol (170 ml) and N,N-dimethylformamide (40 ml); 1H-benzotriazole-1-methanol (2.64 g, 17.7 mmol) was added thereto; and the reaction mixture was heated to reflux for 2 hours. After allowing to be cooled to room temperature, sodium borohydride (1.49 g, 35.4 mmol) was added to the reaction mixture; the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was partitioned between ethyl acetate and water; and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia BW-300, hexane-ethyl acetate-methanol system). The obtained crystals were suspended in acetone: diethyl ether =1:3, filtered off, washed with hexane, and dried to yield the title compound (1.05 g, 3.55 mmol, 20.1%) as pale yellow crystals.

Workup

  1. temperatureand the reaction mixture was heated
  2. temperatureto reflux for 2 hours
  3. customThe reaction mixture was partitioned between ethyl acetate and water
  4. washand the organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (Fuji Silysia BW-300, hexane-ethyl acetate-methanol system)
  8. filtrationdiethyl ether =1:3, filtered off
  9. washwashed with hexane
  10. customdried

Sources & evidence

ORD record
ord-afd3b4c437044e2483fa5196517ccebe
Source dataset
uspto-grants-2008_12
Patent number
US07468380B2

Reaction notes

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