Diethyl Ether → 5-(2-Amino-5-cyanopyridin-4-ylamino)indole-1-carboxylic acid phenylamide

HRID 2215586Notes

Reaction equation

HRID 2215586 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6](Cl)[C:5]([C:9]#[N:10])=[CH:4][N:3]=1.[C:11]1([NH:17][C:18]([N:20]2[C:28]3[C:23](=[CH:24][C:25]([NH2:29])=[CH:26][CH:27]=3)[CH:22]=[CH:21]2)=[O:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.Cl.N1C=CC=CC=1.C(OCC)C>C(OC(O)C)C>[C:11]1([NH:17][C:18]([N:20]2[C:28]3[C:23](=[CH:24][C:25]([NH:29][C:6]4[C:5]([C:9]#[N:10])=[CH:4][N:3]=[C:2]([NH2:1])[CH:7]=4)=[CH:26][CH:27]=3)[CH:22]=[CH:21]2)=[O:19])[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 3283Diethyl Ether2×HCID 10176127Pyridinium chlorideHCID 210548515-Aminoindole-1-carboxylic acid phenylamideHCID 219492196-Amino-4-chloro-3-pyridinecarbonitrile

Product 1

HCID 210548165-(2-Amino-5-cyanopyridin-4-ylamino)indole-1-carboxylic acid phenylamideYield 35.7%

Reagents, catalysts & solvents 1

HCID 101298981-EthoxyethanolSolvent

Conditions

Temperature
130 °C

Procedure

2-Amino-4-chloro-5-cyanopyridine (200 mg, 1.30 mmol, Production example 215-3) was dissolved in ethoxyethanol (13.0 ml); 5-aminoindole-1-carboxylic acid phenylamide (408 mg, 1.62 mmol, Production example 201-2) and pyridine hydrochloride (315 mg, 2.73 mmol) were added thereto; and the reaction mixture was heated and stirred at 130° C. for 4 hours. After cooling to room temperature, the reaction mixture was partitioned between a saturated aqueous solution of sodium hydrogencarbonate and ethyl acetate; 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 NH, hexane:ethyl acetate=2:3, ethyl acetate, ethyl acetate:methanol=95:5 in this order). The pale yellow oil obtained was solidified with diethyl ether; the crystals were suspended with diethyl ether, filtered off, washed with diethyl ether, and dried to yield the title compound (171 mg, 0.464 mmol, 35.7%) as colorless crystals.

Workup

  1. temperatureand the reaction mixture was heated
  2. temperatureAfter cooling to room temperature
  3. customthe reaction mixture was partitioned between a saturated aqueous solution of sodium hydrogencarbonate and ethyl acetate
  4. washthe 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 NH, hexane
  8. customThe pale yellow oil obtained
  9. filtrationfiltered off
  10. washwashed with diethyl ether
  11. customdried

Sources & evidence

ORD record
ord-5e9da17cec1249dfa8da99a8236d065c
Source dataset
uspto-grants-2006_09
Patent number
US07109219B2

Reaction notes

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