Chlorodimethylaluminum → 2-Methyl-4-{[1-(methylsulfonyl)azetidin-3-yl]oxy)-N-(2-methyl-2H-1,2,3-triazol-4-yl)-1-benzofuran-6-carboxamide

HRID 1643772Notes

Reaction equation

HRID 1643772 reaction equation
[CH3:1][N:2]1[N:6]=[C:5]([NH2:7])[CH:4]=[N:3]1.[Al](Cl)(C)C.[CH3:12][C:13]1[O:14][C:15]2[CH:21]=[C:20]([C:22](OCC)=[O:23])[CH:19]=[C:18]([O:27][CH:28]3[CH2:31][N:30]([S:32]([CH3:35])(=[O:34])=[O:33])[CH2:29]3)[C:16]=2[CH:17]=1>ClCCl>[CH3:12][C:13]1[O:14][C:15]2[CH:21]=[C:20]([C:22]([NH:7][C:5]3[CH:4]=[N:3][N:2]([CH3:1])[N:6]=3)=[O:23])[CH:19]=[C:18]([O:27][CH:28]3[CH2:31][N:30]([S:32]([CH3:35])(=[O:34])=[O:33])[CH2:29]3)[C:16]=2[CH:17]=1

Participants

5

Reactant 3

HCID 79147ChlorodimethylaluminumHCID 145364352-Methyl-2H-1,2,3-triazol-4-amineHCID 59560425Ethyl 2-methyl-4-{[1-(methylsulfonyl)azetidin-3-yl]oxy}-1-benzofuran-6-carboxylate

Product 1

HCID 595603392-Methyl-4-{[1-(methylsulfonyl)azetidin-3-yl]oxy)-N-(2-methyl-2H-1,2,3-triazol-4-yl)-1-benzofuran-6-carboxamideYield 68.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-methyl-2H-1,2,3-triazol-4-amine (267 mg, 1.98 mmol) in dichloromethane (5 mL) at 0° C. was added Al(CH3)2Cl (1.98 mL, 1.98 mmol, 1M in hexanes) drop-wise. After the addition, the ice-bath was removed, and the mixture was stirred for 30 minutes at room temperature. Ethyl 2-methyl-4-{[1-(methylsulfonyl)azetidin-3-yl]oxy}-1-benzofuran-6-carboxylate (70 mg, 0.198 mmol) was added and the stirring was continued for 14 h. The reaction was quenched with potassium sodium tartrate tetrahydrate (20% w/w) cautiously. The product was extracted with CH2Cl2, washed with brine and dried over Na2SO4. The product was purified by gradient silica gel chromatography using CHCl3/MeOH (95/5 to 85/15) to give the title compound (55 mg, 68%) as a white solid after evaporation of the solvents. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.51 (s, 3 H) 2.94 (s, 3 H) 4.06-4.15 (m, 3 H) 4.16 (d, J=4.80 Hz, 2 H) 4.39 (dd, J=9.60, 6.32 Hz, 2 H) 5.05-5.23 (m, 1 H) 6.54 (s, 1 H) 6.97 (s, 1 H) 7.54 (s, 1 H) 8.12 (s, 1 H) 8.46 (s, 1 H); MS (ESI, pos): 406.

Workup

  1. additionAfter the addition
  2. customthe ice-bath was removed
  3. waitthe stirring was continued for 14 h
  4. customThe reaction was quenched with potassium sodium tartrate tetrahydrate (20% w/w) cautiously
  5. extractionThe product was extracted with CH2Cl2
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. customThe product was purified by gradient silica gel chromatography

Sources & evidence

ORD record
ord-e8cfbf7877224090b38facc38eb101c4
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

Loading…