Phthalic Anhydride → (E)-3-[6-[(2-carboxybenzoyl)amino]pyridin-3-yl]-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide

HRID 1921057Notes

Reaction equation

HRID 1921057 reaction equation
[C:1]1(=[O:11])[O:6][C:4](=[O:5])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[NH2:12][C:13]1[N:18]=[CH:17][C:16](/[CH:19]=[CH:20]/[C:21]([N:23]([CH3:35])[CH2:24][C:25]2[N:26]([CH3:34])[C:27]3[C:32]([CH:33]=2)=[CH:31][CH:30]=[CH:29][CH:28]=3)=[O:22])=[CH:15][CH:14]=1.C(=O)(O)[O-].[Na+]>C1COCC1>[C:4]([C:3]1[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=1[C:1]([NH:12][C:13]1[N:18]=[CH:17][C:16](/[CH:19]=[CH:20]/[C:21]([N:23]([CH3:35])[CH2:24][C:25]2[N:26]([CH3:34])[C:27]3[C:32]([CH:33]=2)=[CH:31][CH:30]=[CH:29][CH:28]=3)=[O:22])=[CH:15][CH:14]=1)=[O:11])([OH:6])=[O:5]

Participants

5

Reactant 3

HCID 6811Phthalic AnhydrideHCID 516892Sodium BicarbonateHCID 52877203-(6-Aminopyridin-3-Yl)-N-Methyl-N-((1-Methyl-1h-Indol-2-Yl)Methyl)Acrylamide

Product 1

HCID 57440851(E)-3-[6-[(2-carboxybenzoyl)amino]pyridin-3-yl]-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamideYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Phthalic anhydride (0.81 g, 5.48 mmole) was added to a solution of (E)-3-(6-aminopyridin-3-yl)-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide (0.44 g, 1.37 mmole) and sodium bicarbonate (0.58 g, 6.85 mmole) in THF (70 mL) at RT, and the reaction was heated at reflux under nitrogen. After 48 hr, the reaction was concentrated in vacuo and the residue was diluted with water and extracted with ethyl acetate. The combined extracts were dried over Na2SO4 and concentrated. Flash chromatography on silica gel (10% MeOH/CHCl3) gave the title compound (0.10 g, 16%) as a light yellow solid: MS (ES) m/e 469 (M+H)+.

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux under nitrogen
  3. concentrationthe reaction was concentrated in vacuo
  4. additionthe residue was diluted with water
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined extracts were dried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-4e5852120a4543998c37d38a487180d7
Source dataset
uspto-grants-2012_05
Patent number
US08173646B2

Reaction notes

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