Water → methyl 2-[3-cyano-4-(1H-pyrrol-1-yl)phenyl]isonicotinate

HRID 562923Notes

Reaction equation

HRID 562923 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([CH:15]=[CH:16][N:17]=2)[C:11]([O:13][CH3:14])=[O:12])=[CH:4][C:3]=1[C:18]#[N:19].CO[CH:22]1[CH2:26][CH2:25][CH:24](OC)O1.O>C(O)(=O)C>[C:18]([C:3]1[CH:4]=[C:5]([C:8]2[CH:9]=[C:10]([CH:15]=[CH:16][N:17]=2)[C:11]([O:13][CH3:14])=[O:12])[CH:6]=[CH:7][C:2]=1[N:1]1[CH:22]=[CH:26][CH:25]=[CH:24]1)#[N:19]

Participants

5

Reactant 3

HCID 962WaterHCID 790982,5-DimethoxytetrahydrofuranHCID 66995476Methyl 2-(4-amino-3-cyanophenyl)isonicotinate

Product 1

HCID 66995160methyl 2-[3-cyano-4-(1H-pyrrol-1-yl)phenyl]isonicotinate

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

131 mg of methyl 2-(4-amino-3-cyanophenyl)isonicotinate and 67 μl of 2,5-dimethoxytetrahydrofuran were dissolved in 1.3 ml of acetic acid solution, followed by heating and stirring at 100° C. for 4 hours. The solution was poured into water, followed by extraction with ethyl acetate. The solvent of the organic layer was evaporated under reduced pressure, and the residue was purified by column chromatography (hexane:ethyl acetate=10:1 to 1:1) to obtain 100 mg of methyl 2-[3-cyano-4-(1H-pyrrol-1-yl)phenyl]isonicotinate. (2) 100 mg of methyl 2-[3-cyano-4-(1H-pyrrol-1-yl)phenyl]isonicotinate was dissolved in a mixture of 2 ml of methanol and 3 ml of THF, and 66 μl of aqueous 1 M sodium hydroxide solution was added, followed by heating under reflux for 3 hours. The reaction mixture was cooled, then neutralized with 66 μl of 1 M hydrochloric acid, followed by extraction with a mixture of 2-propanol and chloroform (1:4). The organic layer was washed with brine. The solvent of the organic layer was evaporated under reduced pressure, and the resulting residue was recrystallized from a mixture of 2-propanol and chloroform (1:4) to obtain 95 mg of 2-[3-cyano-4-(1H-pyrrol-1-yl)phenyl]isonicotinic acid.

Workup

  1. temperatureby heating
  2. extractionfollowed by extraction with ethyl acetate
  3. customThe solvent of the organic layer was evaporated under reduced pressure
  4. customthe residue was purified by column chromatography (hexane:ethyl acetate=10:1 to 1:1)

Sources & evidence

ORD record
ord-0a8b23fe6bb7462fb08c5cb05380b685
Source dataset
uspto-grants-2011_11
Patent number
US08067446B2

Reaction notes

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