Triethylamine → 4-Benzyloxy-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

HRID 1643584Notes

Reaction equation

HRID 1643584 reaction equation
[CH2:1]([O:8][C:9]1[C:14]2[CH2:15][C:16]([CH3:19])([CH3:18])[O:17][C:13]=2[CH:12]=[C:11]([C:20](O)=[O:21])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[NH2:27][C:28]1[CH:32]=[CH:31][N:30]([CH3:33])[N:29]=1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[CH3:33][N:30]1[CH:31]=[CH:32][C:28]([NH:27][C:20]([C:11]2[CH:10]=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:14]3[CH2:15][C:16]([CH3:19])([CH3:18])[O:17][C:13]=3[CH:12]=2)=[O:21])=[N:29]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 1372541-Methyl-3-aminopyrazoleHCID 595600094-Benzyloxy-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid

Product 1

HCID 595599654-Benzyloxy-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amideYield 60.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-benzyloxy-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (77b) (6.98 g, 23.40 mmol) in CH2Cl2 (100 mL) was added thionyl chloride (2.04 mL, 28.1 mmol), followed by 10 drops of DMF. The mixture was refluxed for 2 h, then concentrated and dried under vacuum. The residue was dissolved in CH2Cl2 (100 mL), and 3-amino-1-methyl-pyrazole (2.73 g, 28.1 mmol) was added at 0° C., followed by triethylamine (6.52 ml, 46.80 mmol). The mixture was stirred at 0° C. to room temperature for 1 hr. The reaction was quenched with H2O, extracted with 3×CH2Cl2. The combined organic layers were dried over Na2SO4, concentrated and purified by flash column chromatography with 1-3% MeOH in CHCl3 to give a white solid (5.31 g, 60% yield). 1H NMR (400 MHz, CDCl3) δ 8.43 (s, 1 H) 7.29-7.50 (m, 6 H) 7.09 (d, J=1.01 Hz, 1 H) 6.84 (dd, J=8.08, 1.77 Hz, 2 H) 5.14 (s, 2 H) 3.83 (s, 3 H) 2.95-3.06 (m, 2 H) 1.50 (s, 6 H); LCMS for C22H23N3O3 m/z 378.20 (M+H+).

Workup

  1. temperatureThe mixture was refluxed for 2 h
  2. concentrationconcentrated
  3. customdried under vacuum
  4. dissolutionThe residue was dissolved in CH2Cl2 (100 mL)
  5. customThe reaction was quenched with H2O
  6. extractionextracted with 3×CH2Cl2
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. concentrationconcentrated
  9. custompurified by flash column chromatography with 1-3% MeOH in CHCl3

Sources & evidence

ORD record
ord-bf3d683f7fed43a68b7d2e331ea58ad1
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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