Water → 2-Cyclopropanecarbonyl-7-methoxybenzofuran-4-carboxylic Acid (3-methylpyridin-4-yl)amide

HRID 1108314Notes

Reaction equation

HRID 1108314 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[CH3:8].C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[N+](C1C=CC([O:28][C:29]([C:31]2[CH:32]=[CH:33][C:34]([O:45][CH3:46])=[C:35]3[O:39][C:38]([C:40]([CH:42]4[CH2:44][CH2:43]4)=[O:41])=[CH:37][C:36]=23)=O)=CC=1)([O-])=O.O>CN(C)C=O>[CH3:8][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:2]=1[NH:1][C:29]([C:31]1[CH:32]=[CH:33][C:34]([O:45][CH3:46])=[C:35]2[O:39][C:38]([C:40]([CH:42]3[CH2:43][CH2:44]3)=[O:41])=[CH:37][C:36]=12)=[O:28]

Participants

6

Reactant 4

HCID 962WaterHCID 748113-Methyl-4-pyridinamineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 541277062-Cyclopropanecarbonyl-7-methoxybenzofuran-4-carboxylic Acid 4-nitrophenyl Ester

Product 1

HCID 544624842-Cyclopropanecarbonyl-7-methoxybenzofuran-4-carboxylic Acid (3-methylpyridin-4-yl)amideYield 50.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-amino-3-methylpyridine (160 mg) in dimethylformamide (10 ml) under an atmosphere of nitrogen was added sodium hexamethyldisilazide (1.0M solution in tetrahydrofuran, 1.5 ml). The reaction mixture was stirred at room temperature for 10 minutes. 2-Cyclopropanecarbonyl-7-methoxy-benzofuran-4-carboxylic acid 4-nitrophenyl ester (280 mg) was then added and stirring continued for 18 h. Water (10 ml) was added and the solvent was removed in vacuo. The residue was dissolved in ethyl acetate (150 ml), washed with water (3×50 ml) and washed with brine (50 ml). The combined aqueous layers were extracted with dichloromethane (2×50 ml), the organic layers were combined, dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by flash chromatography on silica eluting with 5% methanol in dichloromethane followed by trituration with diethyl ether afforded the title compound as an off-white solid (130 mg).

Workup

  1. stirringstirring
  2. waitcontinued for 18 h
  3. customthe solvent was removed in vacuo
  4. dissolutionThe residue was dissolved in ethyl acetate (150 ml)
  5. washwashed with water (3×50 ml)
  6. washwashed with brine (50 ml)
  7. extractionThe combined aqueous layers were extracted with dichloromethane (2×50 ml)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by flash chromatography on silica eluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-1cfc993ea2af4642a5d2075b3070aa09
Source dataset
uspto-grants-2000_05
Patent number
US06066657

Reaction notes

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