Dimethylamine, hydrochloride → Ethyl 2-(dimethylcarbamoyl)-4-(4-(methylsulfonyl)phenoxy)-benzofuran-6-carboxylate

HRID 1643753Notes

Reaction equation

HRID 1643753 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:17]=[C:16]([O:18][C:19]2[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=2)[C:9]2[CH:10]=[C:11]([C:13](O)=[O:14])[O:12][C:8]=2[CH:7]=1)=[O:5])[CH3:2].[CH3:29][N:30](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)[CH3:31].F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.CNC>CN(C=O)C.O>[CH3:29][N:30]([CH3:31])[C:13]([C:11]1[O:12][C:8]2[CH:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH:17]=[C:16]([O:18][C:19]3[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)[C:9]=2[CH:10]=1)=[O:14]

Participants

7

Reactant 4

HCID 10473Dimethylamine, hydrochlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 667562256-(Ethoxycarbonyl)-4-(4-(methylsulfonyl)phenoxy)benzofuran-2-carboxylic acid

Product 1

HCID 66755872Ethyl 2-(dimethylcarbamoyl)-4-(4-(methylsulfonyl)phenoxy)-benzofuran-6-carboxylateYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6-(ethoxycarbonyl)-4-(4-(methylsulfonyl)phenoxy)benzofuran-2-carboxylic acid (450 mg, 1.11 mmol) in DMF (10 mL) was added HATU (846 mg, 2.23 mmol), DIEA (719 mg, 5.56 mmol) and the solution was stirred at 0° C. for 15 min. Dimethylamine hydrochloride (136 mg, 1.67 mmol) was added and the solution was warmed gradually to room temperature and stirred for 14 h. Water was added and the product was extracted with CHCl3. The combined organic layers were washed with water (2×), brine, dried over Na2SO4, and concentrated. The product was purified by gradient silica gel chromatography using CHCl3/MeOH (100/0 to 95/5) to give the title compound (460 mg, 96%) as a light yellow solid. 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 1.40 (t, J=7.16 Hz, 3 H) 3.07 (s, 3 H) 3.13 (s, 3 H) 3.33 (s, 3 H) 4.40 (q, J=7.16 Hz, 2 H) 7.07-7.15 (m, 2 H) 7.16 (d, J=0.75 Hz, 1 H) 7.65 (d, J=0.94 Hz, 1 H) 7.87-7.94 (m, 2H) 8.10-8.15 (d, J=0.94 Hz, 1 H).

Workup

  1. temperaturethe solution was warmed gradually to room temperature
  2. stirringstirred for 14 h
  3. extractionthe product was extracted with CHCl3
  4. washThe combined organic layers were washed with water (2×), brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe product was purified by gradient silica gel chromatography

Sources & evidence

ORD record
ord-fe90dd5b6462400dbcd2e0866293c818
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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