Pyridine → 2-[5-(4-Fluoro-benzyloxy)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-acetamide

HRID 431579Notes

Reaction equation

HRID 431579 reaction equation
[F:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][O:7][C:8]2[CH:9]=[C:10]([C:17]([OH:19])=O)[C:11](=[CH:15][CH:16]=2)[C:12]([OH:14])=O)=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:35][CH2:36][C:37]([NH2:39])=[O:38].N1C=CC=CC=1>CN1CCCC1=O.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][O:7][C:8]2[CH:9]=[C:10]3[C:11](=[CH:15][CH:16]=2)[C:12](=[O:14])[N:35]([CH2:36][C:37]([NH2:39])=[O:38])[C:17]3=[O:19])=[CH:20][CH:21]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 682631,1'-CarbonyldiimidazoleHCID 2723639Glycinamide hydrochlorideHCID 223970954-(4-Fluoro-benzyloxy)-phthalic acid

Product 1

HCID 101257982-[5-(4-Fluoro-benzyloxy)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-acetamideYield 69.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 4-(4-fluoro-benzyloxy)-phthalic acid (185 mg, 0.64 mmol) and carbonyldiimidazole (109 mg, 0.67 mmol) in 1-methyl-2-pyrrolidinone (4 mL) was stirred at room temperature for 10 min and then heated at 50° C. for 15 min. To this mixture was added glycinamide hydrochloride (78 mg, 0.71 mmol) and pyridine (50 mg, 0.63 mmol) and the resulting mixture heated at 175 or 200° C. with microwave radiation (Smith reactor) for 10 min. After cooling to room temperature, the mixture was diluted with water and the resulting precipitate was filtered off and purified by chromatography (SiO2, CH2Cl2:2N NH3/MeOH 9:1) to afford the title compound (146 mg, 69%) as a white solid. MS: m/e=329.3. (M+H+).

Workup

  1. temperatureheated at 50° C. for 15 min
  2. temperaturethe resulting mixture heated at 175 or 200° C. with microwave radiation (Smith reactor) for 10 min
  3. temperatureAfter cooling to room temperature
  4. filtrationthe resulting precipitate was filtered off
  5. custompurified by chromatography (SiO2, CH2Cl2:2N NH3/MeOH 9:1)

Sources & evidence

ORD record
ord-1a09e04e2ca04a40804198dcec40000a
Source dataset
uspto-grants-2003_12
Patent number
US06660736B2

Reaction notes

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