2-Amino-5-methylpyridine → 2-(Hydroxymethyl)-N-(5-methylpyridin-2-yl)-4-(4-(methylsulfonyl)-phenoxy)benzofuran-6-carboxamide

HRID 1177285Notes

Reaction equation

HRID 1177285 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[Cl-].C[Al+]C.[OH:13][CH2:14][C:15]1[O:16][C:17]2[CH:23]=[C:22]([C:24](OCC)=[O:25])[CH:21]=[C:20]([O:29][C:30]3[CH:35]=[CH:34][C:33]([S:36]([CH3:39])(=[O:38])=[O:37])=[CH:32][CH:31]=3)[C:18]=2[CH:19]=1>ClCCCl>[OH:13][CH2:14][C:15]1[O:16][C:17]2[CH:23]=[C:22]([C:24]([NH:1][C:2]3[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=3)=[O:25])[CH:21]=[C:20]([O:29][C:30]3[CH:31]=[CH:32][C:33]([S:36]([CH3:39])(=[O:38])=[O:37])=[CH:34][CH:35]=3)[C:18]=2[CH:19]=1

Participants

5

Reactant 3

HCID 153482-Amino-5-methylpyridineHCID 16686359Dimethylalumanylium chlorideHCID 66755904Ethyl 2-(hydroxymethyl)-4-(4-(methylsulfonyl)phenoxy)benzofuran-6-carboxylate

Product 1

HCID 667556442-(Hydroxymethyl)-N-(5-methylpyridin-2-yl)-4-(4-(methylsulfonyl)-phenoxy)benzofuran-6-carboxamideYield 71%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 2-amino-5-methylpyridine (305 mg, 2.82 mmol) in DCE (10 mL) at 0° C. was added dimethylaluminum chloride (1M in hexanes, 2.82 mL) drop-wise. After the addition, the ice-bath was removed, and the mixture was stirred for 30 minutes at room temperature. Ethyl 2-(hydroxymethyl)-4-(4-(methylsulfonyl)phenoxy)benzofuran-6-carboxylate (110 mg, 0.282 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 (90 mg, 71%) as a white solid. 1 H NMR (300 MHz, DMSO-D6) δ ppm 2.27 (s, 3 H) 3.20 (s, 3 H) 4.58 (d, J=5.84 Hz, 2 H) 5.60 (t, J=5.84 Hz, 1 H) 6.61 (s, 1 H) 7.24 (d, J=8.67 Hz, 2 H) 7.66 (dd, J=8.48, 2.26 Hz, 1 H) 7.70 (s, 1 H) 7.93 (d, J=8.67 Hz, 2 H) 8.06 (d, J=8.48 Hz, 1 H) 8.22 (d, J=2.26 Hz, 1 H) 8.24 (s, 1 H) 10.83 (s, 1 H). LCMS m/z 453.0 (M+H)+.

Workup

  1. additionAfter the addition
  2. customthe ice-bath was removed
  3. waitthe stirring was continued for another 14 h
  4. customThe reaction was quenched with potassium sodium tartrate tetrahydrate (20% w/w) cautiously
  5. extractionThe product was extracted with CHCl3
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. customThe product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-4382d3361f5346448b613a09c4717e6b
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

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