Pyrrolidine → 2-Methyl-6-{[7-(2-pyrrolidin-1-ylethoxy)quinolin-4-yl]oxy}-1-benzofuran-3-carboxylic acid

HRID 130674Notes

Reaction equation

HRID 130674 reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([O:15][C:16]3[CH:29]=[CH:28][C:19]4[C:20]([C:24]([O:26]C)=[O:25])=[C:21]([CH3:23])[O:22][C:18]=4[CH:17]=3)=[CH:10][CH:11]=[N:12]2)=[CH:7][CH:6]=1.[NH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1>CN(C=O)C>[CH3:23][C:21]1[O:22][C:18]2[CH:17]=[C:16]([O:15][C:9]3[C:8]4[C:13](=[CH:14][C:5]([O:4][CH2:3][CH2:2][N:30]5[CH2:34][CH2:33][CH2:32][CH2:31]5)=[CH:6][CH:7]=4)[N:12]=[CH:11][CH:10]=3)[CH:29]=[CH:28][C:19]=2[C:20]=1[C:24]([OH:26])=[O:25]

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 59730755Methyl 6-{[7-(2-bromoethoxy)quinolin-4-yl]oxy}-2-methyl-1-benzofuran-3-carboxylate

Product 1

HCID 597307642-Methyl-6-{[7-(2-pyrrolidin-1-ylethoxy)quinolin-4-yl]oxy}-1-benzofuran-3-carboxylic acidYield 14.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 6-[(7-hydroxyquinolin-4-yl)oxy]-2-methyl-1-benzofuran-3-carboxylate 121-D (2.4 g, 7.2 mmol) in DMF (20 ml) was added K2CO3 (5 g, 35.8 mmol) a dibromoethane (2.7 g, 14.3 mmol). The reaction mixture was stirred at room temperature overnight. Column chromatography gave methyl 6-{[7-(2-bromoethoxy)quinolin-4-yl]oxy}-2-methyl-1-benzofuran-3-carboxylate 121-E (1.5 g). A solution of compound 121-E (750 mg) and pyrrolidine (351 mg) in DMF (3 ml) was heated to 60° C. for 45 min. The reaction mixture was extracted with EtOAc. Methyl 2-methyl-6-{[7-(2-pyrrolidin-1-ylethoxy)quinolin-4-yl]oxy}benzofuran-3-carboxylate 121-F (110 mg) was purified by silica gel chromatography using 5-10% MeOH/CH2Cl2. Compound 121-F (110 mg) was treated with 20% NaOH (1 ml) in MeOH (1 ml) overnight. The reaction mixture was acidified with AcOH and extracted with EtOAc. The residue was purified by silica gel chromatography using 0-10% MeOH in CH2Cl2 to give 2-methyl-6-{[7-(2-pyrrolidin-1-ylethoxy)quinolin-4-yl]oxy}-1-benzofuran-3-carboxylic acid 121-G (100 mg).

Workup

  1. extractionThe reaction mixture was extracted with EtOAc
  2. customMethyl 2-methyl-6-{[7-(2-pyrrolidin-1-ylethoxy)quinolin-4-yl]oxy}benzofuran-3-carboxylate 121-F (110 mg) was purified by silica gel chromatography
  3. additionCompound 121-F (110 mg) was treated with 20% NaOH (1 ml) in MeOH (1 ml) overnight
  4. extractionextracted with EtOAc
  5. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-1dff45b62a214f86beccd4b97c704a1e
Source dataset
uspto-grants-2008_06
Patent number
US07381824B2

Reaction notes

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