2-Amino-5-methylpyridine → N2,N2-Dimethyl-N6-(5-methylpyridin-2-yl)-4-(4-(methylsulfonyl)-phenoxy)-benzofuran-2,6-dicarboxamide

HRID 1643749Notes

Reaction equation

HRID 1643749 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[Al](Cl)(C)C.[CH3:13][N:14]([CH3:42])[C:15]([C:17]1[O:18][C:19]2[CH:25]=[C:24]([C:26](OCC)=[O:27])[CH:23]=[C:22]([O:31][C:32]3[CH:37]=[CH:36][C:35]([S:38]([CH3:41])(=[O:40])=[O:39])=[CH:34][CH:33]=3)[C:20]=2[CH:21]=1)=[O:16]>ClCCCl>[CH3:13][N:14]([CH3:42])[C:15]([C:17]1[O:18][C:19]2[CH:25]=[C:24]([C:26]([NH:1][C:2]3[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=3)=[O:27])[CH:23]=[C:22]([O:31][C:32]3[CH:37]=[CH:36][C:35]([S:38]([CH3:41])(=[O:40])=[O:39])=[CH:34][CH:33]=3)[C:20]=2[CH:21]=1)=[O:16]

Participants

5

Reactant 3

HCID 153482-Amino-5-methylpyridineHCID 79147ChlorodimethylaluminumHCID 66755872Ethyl 2-(dimethylcarbamoyl)-4-(4-(methylsulfonyl)phenoxy)-benzofuran-6-carboxylate

Product 1

HCID 66755862N2,N2-Dimethyl-N6-(5-methylpyridin-2-yl)-4-(4-(methylsulfonyl)-phenoxy)-benzofuran-2,6-dicarboxamideYield 61%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

2-Amino-5-methyl pyridine (226 mg, 2.09 mmol) was dissolved in DCE (10 mL) at 0° C., and Al(CH3)2Cl (2.09 mL, 1M in hexanes) was then added drop-wise. After stirring the mixture at room temperature for 30 minutes, ethyl 2-(dimethylcarbamoyl)-4-(4-(methylsulfonyl)phenoxy)-benzofuran-6-carboxylate (90 mg, 0.21 mmol) was then 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 (61 mg, 61%) as a white solid. 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 2.32 (s, 3 H) 3.08 (s, 3 H) 3.15 (s, 3 H) 3.34 (s, 3 H) 7.12-7.18 (m, 2 H) 7.19 (s, 1 H) 7.58 (dd, J=8.48, 2.26 Hz, 1 H) 7.87-7.98 (m, 2 H) 7.99 (s, 1 H) 8.11 (s, 1 H) 8.24 (d, J=8.48 Hz, 1 H) 8.64 (s, 1 H). LCMS m/z 494.0 (M+H)+.

Workup

  1. waitthe stirring was continued for another 14 h
  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-4d78bb57477f41aca977499e1de9e998
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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