1-Ethoxyethanol → N1-Methyl-5-(2-amino-5-cyano-4-pyridyl)amino-1H-1-indolecarboxamide

HRID 2376926Notes

Reaction equation

HRID 2376926 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6](Cl)[C:5]([C:9]#[N:10])=[CH:4][N:3]=1.C(OC(O)C)C.Cl.N1C=CC=CC=1.[CH3:24][NH:25][C:26]([N:28]1[C:36]2[C:31](=[CH:32][C:33]([NH2:37])=[CH:34][CH:35]=2)[CH:30]=[CH:29]1)=[O:27]>>[CH3:24][NH:25][C:26]([N:28]1[C:36]2[C:31](=[CH:32][C:33]([NH:37][C:6]3[C:5]([C:9]#[N:10])=[CH:4][N:3]=[C:2]([NH2:1])[CH:7]=3)=[CH:34][CH:35]=2)[CH:30]=[CH:29]1)=[O:27]

Participants

5

Reactant 4

HCID 101298981-EthoxyethanolHCID 10176127Pyridinium chlorideHCID 21949101N1-Methyl-5-amino-1H-1-indolecarboxamideHCID 219492196-Amino-4-chloro-3-pyridinecarbonitrile

Product 1

HCID 21949356N1-Methyl-5-(2-amino-5-cyano-4-pyridyl)amino-1H-1-indolecarboxamideYield 44.9%

Conditions

Temperature
130 °C

Procedure

2-Amino-4-chloro-5-cyanopyridine (123 mg, 0.80 mmol) synthesized in Production example 215-3, ethoxyethanol (3 ml) and pyridine hydrochloride (186 mg, 1.60 mmol) were added to N1-methyl-5-amino-1H-1-indolecarboxamide (198 mg, 1.05 mmol) synthesized in Production example 218-2; and the reaction mixture was stirred at 130° C. for 3 hours. After allowing to be cooled to room temperature, the reaction mixture was partitioned between a saturated aqueous solution of sodium hydrogencarbonate and ethyl acetate; and the organic layer was washed with water and brine, dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (hexane-ethyl acetate, ethyl acetate in this order) to yield the title compound (110 mg, 0.359 mmol).

Workup

  1. customsynthesized in Production example 218-2
  2. temperatureto be cooled to room temperature
  3. customthe reaction mixture was partitioned between a saturated aqueous solution of sodium hydrogencarbonate and ethyl acetate
  4. washand the organic layer was washed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off
  7. customthe residue was purified by silica gel column chromatography (hexane-ethyl acetate, ethyl acetate in this order)

Sources & evidence

ORD record
ord-962b24c8c9854f3e80198bfc208d5633
Source dataset
uspto-grants-2008_12
Patent number
US07468380B2

Reaction notes

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