Chlorodimethylaluminum → N-(1-Methyl-1H-pyrazol-3-yl)-4-[4-(methylsulfonyl)phenoxy]-2-[(2-oxopyrrolidin-1-yl)methyl]-1-benzofuran-6-carboxamide

HRID 1643760Notes

Reaction equation

HRID 1643760 reaction equation
[NH2:1][C:2]1[CH:6]=[CH:5][N:4]([CH3:7])[N:3]=1.[Al](Cl)(C)C.[CH3:12][S:13]([C:16]1[CH:43]=[CH:42][C:19]([O:20][C:21]2[C:26]3[CH:27]=[C:28]([CH2:30][N:31]4[CH2:35][CH2:34][CH2:33][C:32]4=[O:36])[O:29][C:25]=3[CH:24]=[C:23]([C:37](OCC)=[O:38])[CH:22]=2)=[CH:18][CH:17]=1)(=[O:15])=[O:14]>ClCCCl>[CH3:7][N:4]1[CH:5]=[CH:6][C:2]([NH:1][C:37]([C:23]2[CH:22]=[C:21]([O:20][C:19]3[CH:42]=[CH:43][C:16]([S:13]([CH3:12])(=[O:14])=[O:15])=[CH:17][CH:18]=3)[C:26]3[CH:27]=[C:28]([CH2:30][N:31]4[CH2:35][CH2:34][CH2:33][C:32]4=[O:36])[O:29][C:25]=3[CH:24]=2)=[O:38])=[N:3]1

Participants

5

Reactant 3

HCID 79147ChlorodimethylaluminumHCID 1372541-Methyl-3-aminopyrazoleHCID 66755917Ethyl 4-(4-(methylsulfonyl)phenoxy)-2-((2-oxopyrrolidin-1-yl)methyl)benzofuran-6-carboxylate

Product 1

HCID 66755887N-(1-Methyl-1H-pyrazol-3-yl)-4-[4-(methylsulfonyl)phenoxy]-2-[(2-oxopyrrolidin-1-yl)methyl]-1-benzofuran-6-carboxamideYield 47%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 3-amino-1-methyl pyrazole (106 mg, 1.09 mmol) in DCE (10 mL) at 0° C. was added Al(CH3)2Cl (1.09 mL, 1M in hexanes) drop-wise. After removal of the ice-bath, the mixture was stirred for min at room temperature. Ethyl 4-(4-(methylsulfonyl)phenoxy)-2-((2-oxopyrrolidin-1-yl)methyl)benzofuran-6-carboxylate (50 mg, 0.11 mmol) was added and the stirring was continued for another 14 h. The reaction was quenched with potassium sodium tartrate tetrahydrate (20% w/w) cautiously. The product was extracted with CHCl3, washed with brine and dried over MgSO4. The product was purified by reverse phase HPLC to give the title compound (22 mg, 47%) as a white solid. 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 1.97-2.13 (m, 2 H) 2.44 (t, J=8.01 Hz, 2 H) 3.08 (s, 3 H) 3.46 (t, J=6.97 Hz, 2 H) 3.81 (s, 3 H) 4.60 (s, 2 H) 6.54 (s, 1 H) 6.79 (d, J=2.26 Hz, 1 H) 7.09-7.17 (m, 2 H) 7.29 (d, J=2.26 Hz, 1 H) 7.44 (s, 1 H) 7.81-7.98 (m, 3 H) 8.54 (s, 1 H). LCMS m/z 509.0 (M+H)+.

Workup

  1. customAfter removal of the ice-bath
  2. customThe reaction was quenched with potassium sodium tartrate tetrahydrate (20% w/w) cautiously
  3. extractionThe product was extracted with CHCl3
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. customThe product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-afed26fe3e80418dba9a059cd5b4580a
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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