Chlorodimethylaluminum → 4-{4-[(Dimethylamino)sulfonyl]-3-fluorophenoxy)-N-(4-methoxypyridin-2-yl)-2-methyl-1-benzofuran-6-carboxamide

HRID 1643754Notes

Reaction equation

HRID 1643754 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH2:9])[CH:4]=1.[Al](Cl)(C)C.[CH3:14][N:15]([CH3:42])[S:16]([C:19]1[CH:40]=[CH:39][C:22]([O:23][C:24]2[C:29]3[CH:30]=[C:31]([CH3:33])[O:32][C:28]=3[CH:27]=[C:26]([C:34](OCC)=[O:35])[CH:25]=2)=[CH:21][C:20]=1[F:41])(=[O:18])=[O:17]>ClCCCl.C(Cl)Cl>[CH3:42][N:15]([CH3:14])[S:16]([C:19]1[CH:40]=[CH:39][C:22]([O:23][C:24]2[C:29]3[CH:30]=[C:31]([CH3:33])[O:32][C:28]=3[CH:27]=[C:26]([C:34]([NH:9][C:5]3[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=[CH:7][N:6]=3)=[O:35])[CH:25]=2)=[CH:21][C:20]=1[F:41])(=[O:17])=[O:18]

Participants

6

Reactant 3

HCID 79147ChlorodimethylaluminumHCID 108987152-Amino-4-MethoxypyridineHCID 59560433Ethyl 4-{4-[(dimethylamino)sulfonyl]-3-fluorophenoxy}-2-methyl-1-benzofuran-6-carboxylate

Product 1

HCID 595604504-{4-[(Dimethylamino)sulfonyl]-3-fluorophenoxy)-N-(4-methoxypyridin-2-yl)-2-methyl-1-benzofuran-6-carboxamideYield 93%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-methoxypyridin-2-amine (295 mg, 2.37 mmol) in DCE at 0° C. was added Al(CH3)2Cl (3.0 mL, 1.0M) drop wise, and the reaction was stirred for 20 minutes at room temperature. Ethyl 4-{4-[(dimethylamino)sulfonyl]-3-fluorophenoxy}-2-methyl-1-benzofuran-6-carboxylate (100 mg, 0.24 mmol) was then added and the reaction was stirred at room temperature for an additional 14 hours. The sample was diluted with CH2Cl2 and quenched with potassium sodium tartrate tetrahydrate (20% w/w) (1 mL). The organic layer was washed with brine and dried over Na2SO4 and concentrated under reduced pressure. The crude sample was introduced into a silica gel column and eluted with MeOH/CHCl3 (5/95-10/90) to provide the product (110 mg, 93% yield) as white solid. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.49 (s, 3 H) 2.84 (d, J=1.51 Hz, 6 H) 3.91 (s, 3 H) 6.26 (s, 1 H) 6.64 (dd, J=5.75, 2.35 Hz, 1 H) 6.71-6.91 (m, 2 H) 7.52 (s, 1 H) 7.81 (t, J=8.29 Hz, 1 H) 7.91 (s, 1 H) 8.01 (s, 1 H) 8.09 (d, J=5.84 Hz, 1 H) 8.59 (s, 1 H); MS (ESI, pos): 500.

Workup

  1. stirringthe reaction was stirred at room temperature for an additional 14 hours
  2. customquenched with potassium sodium tartrate tetrahydrate (20% w/w) (1 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. additionThe crude sample was introduced into a silica gel column
  7. washeluted with MeOH/CHCl3 (5/95-10/90)

Sources & evidence

ORD record
ord-e2ad36c21ad14963af7d3550d910b76a
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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