2-Dimethylaminopyridine → 5-Oxo-pyrrolidine-2-carboxylic acid (3-bromo-2-hydroxy-5-methoxy-phenyl)-amide

HRID 1824793Notes

Reaction equation

HRID 1824793 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([Br:10])[C:3]=1[OH:11].C(N=C=N)C.[OH:17]N1C2C=CC=CC=2N=N1.CN(C1C=CC=CN=1)C.CO[C:38]1[CH:43]=[C:42]([CH2:44][NH:45]CCCNCCCCNCCCN)C=C[C:39]=1[OH:59].O=C1CCNC1C(O)=O>C(Cl)Cl>[Br:10][C:4]1[C:3]([OH:11])=[C:2]([NH:1][C:39]([CH:38]2[CH2:43][CH2:42][C:44](=[O:17])[NH:45]2)=[O:59])[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=1

Participants

7

Reactant 5

HCID 218852-DimethylaminopyridineHCID 757711-HydroxybenzotriazoleHCID 111719822-Amino-6-Bromo-4-MethoxyphenolHCID 12973440EthylcarbodiimideHCID 131725757DL-5 oxo-pyrrolidine-2-carboxylic acid

Product 1

HCID 865924545-Oxo-pyrrolidine-2-carboxylic acid (3-bromo-2-hydroxy-5-methoxy-phenyl)-amideYield 102.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-Amino-6-bromo-4-methoxy-phenol (0.40 g), 1,3-dimethylaminopropyl)-3-ethylcarbodiimide (1.06 g), 1-hydroxybenzotriazole (0.50 g), dimethylaminopyridine (0.22 g) and DL-5-oxo-pyrrolidine-2-carboxylic acid (0.25 g) were reacted together in methylene chloride (7.3 mL). After 3 h, the reaction was diluted with methylene chloride (10 mL) and washed successively with 1N HCl (10 mL), sat. aq. NaHCO3 (10 mL), sat. aq. NaCl (10 mL). The organic layer was dried over sodium sulfate, filtered through celite and concentrated. Chromatography on silica gel (eluant: 0 to 20% methanol:methylene chloride) afforded 5-oxo-pyrrolidine-2-carboxylic acid (3-bromo-2-hydroxy-5-methoxy-phenyl)-amide (0.18 g). MS: 370.2 (100%), 372.2 (90%) (MH+); HPLC tR: 1.51 min. 5-Oxo-pyrrolidine-2-carboxylic acid (3-bromo-2-hydroxy-5-methoxy-phenyl)-amide was cyclized according to synthetic method R to obtain the title compound (0.09 g) after purification on silica gel (eluant: 0 to 30% methanol:methylene chloride). MS: 352.2 (100%), 354.2 (95%) (MH++CH3CN), 311.2 (20%), 313.2 (20%) (MH+).; HPLC tR: 1.84 min.

Workup

  1. washwashed successively with 1N HCl (10 mL), sat. aq. NaHCO3 (10 mL), sat. aq. NaCl (10 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered through celite and
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-80eb094478c94e89a16c10eca3950c1f
Source dataset
uspto-grants-2006_05
Patent number
US07045539B2

Reaction notes

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