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

HRID 1070681Notes

Reaction equation

HRID 1070681 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-f00389074d7642a98b1935b65c79b270
Source dataset
uspto-grants-2005_06
Patent number
US06903095B2

Reaction notes

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