4-Methylmorpholine → 7-Methoxy-2,2-dimethyl-N-(1-methyl-1H-pyrazol-3-yl)-2,3-dihydrobenzofuran-5-carboxamide

HRID 1177369Notes

Reaction equation

HRID 1177369 reaction equation
[CH3:1][O:2][C:3]1[C:11]2[O:10][C:9]([CH3:13])([CH3:12])[CH2:8][C:7]=2[CH:6]=[C:5]([C:14]([OH:16])=O)[CH:4]=1.CCN=C=NCCCN(C)C.CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.[CH3:45][N:46]1[CH:50]=[CH:49][C:48]([NH2:51])=[N:47]1>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:11]2[O:10][C:9]([CH3:12])([CH3:13])[CH2:8][C:7]=2[CH:6]=[C:5]([C:14]([NH:51][C:48]2[CH:49]=[CH:50][N:46]([CH3:45])[N:47]=2)=[O:16])[CH:4]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 1372541-Methyl-3-aminopyrazoleHCID 595602947-Methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-carboxylic acid

Product 1

HCID 595599147-Methoxy-2,2-dimethyl-N-(1-methyl-1H-pyrazol-3-yl)-2,3-dihydrobenzofuran-5-carboxamideYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-carboxylic acid (24 g, 0.11 mol) in CH2Cl2 (500 mL) were added EDCI (31.6 g, 1.08 mol), NMM (54.5 g, 0.54 mol), HOBt (22 g, 0.16 mol) and 1-methyl-1H-pyrazol-3-ylamine (11 g, 0.11 mol) sequentially. The mixture was stirred at room temperature overnight. TLC (EtOAc/petroleum ether=1/1) showed the reaction was complete. The mixture was washed with water (250 mL), sat. aq. citric acid (250 mL×2), sat. NaHCO3 (250 mL) and brine (250 mL) sequentially. The organic phase was dried over Na2SO4 and concentrated to give a white solid. The crude solid was purified by column chromatography (EtOAc/petroleum ether=1/10˜1/1) to give the title compound (9.6 g, 30%) as a white solid. 1H NMR (400 MHz, DMSO): δ 10.49 (s, 1H), 7.49 (s, 1H), 7.44 (s, 2H), 6.48 (s, 1H), 3.74 (s, 3H), 3.69 (s, 3H), 2.96 (s, 2H), 1.35 (s, 6H).

Workup

  1. washThe mixture was washed with water (250 mL), sat. aq. citric acid (250 mL×2), sat. NaHCO3 (250 mL) and brine (250 mL) sequentially
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated
  4. customto give a white solid
  5. customThe crude solid was purified by column chromatography (EtOAc/petroleum ether=1/10˜1/1)

Sources & evidence

ORD record
ord-1c73b7fbd6cf4eba9bebc730332f006b
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

Loading…