Sodium hydride → 5-Benzyloxy-1-[3-(3-bromopyridin-4-yl)propyl]-3-(4-methylthiazol-2-yl)-1H-pyridin-2-one

HRID 367006Notes

Reaction equation

HRID 367006 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:16]2[S:17][CH:18]=[C:19]([CH3:21])[N:20]=2)[C:12](=[O:15])[NH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Br-].[Li+].Br[CH2:27][CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][N:33]=[CH:32][C:31]=1[Br:36]>CN(C=O)C.COCCOC>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:16]2[S:17][CH:18]=[C:19]([CH3:21])[N:20]=2)[C:12](=[O:15])[N:13]([CH2:27][CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][N:33]=[CH:32][C:31]=2[Br:36])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 82050Lithium BromideHCID 110332153-Bromo-4-(3-bromopropyl)pyridineHCID 1354930145-Benzyloxy-3-(4-methylthiazol-2-yl)-1H-pyridin-2-one

Product 1

HCID 109946665-Benzyloxy-1-[3-(3-bromopyridin-4-yl)propyl]-3-(4-methylthiazol-2-yl)-1H-pyridin-2-oneYield 83%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Prepared by a modification of the procedure reported in Tetrahedron Lett., 1995, 8917. 5-Benzyloxy-3-(4-methylthiazol-2-yl)-1H-pyridin-2-one (3.3 mmol) was dissolved in DMF (5 ml) and DME (20 ml). The reaction mixture was cooled to 0° C. and treated with sodium hydride (3.5 mmol). After 10 min, the reaction mixture was treated with lithium bromide (6.6 mmol) and stirred for 15 min at room temperature. The reaction mixture was treated with a solution of 4-(3-bromopropyl)-3-bromopyridine (5.0 mmol) in DME (5 ml) and then it was heated at 75° C. for 60 h. The reaction mixture was cooled, acidified, and washed with ethyl acetate. The aqueous layer was basified and extracted with ethyl acetate. The organic extracts were dried (MgSO4), filtered, and evaporated in vacuo. Purification by column chromatography gave the product as a yellow foam (2.74 mmol, 82%). δH (250 MHz; CDCl3) 8.65 (1H, s), 8.60 (1H, brd), 8.41 (1H, d, J=7.1), 7.40-7.33 (5H, m), 7.16 (1H, d, J=7.3), 7.03 (1H, s), 7.00 (1H, d, J=4.6), 5.02 (2H, s), 4.13 (2H, t, J=10.4), 2.79-2.72 (2H, m), 2.53 (3H, s), 2.17-2.04 (2H, m).

Workup

  1. customPrepared by a modification of the procedure
  2. temperatureit was heated at 75° C. for 60 h
  3. temperatureThe reaction mixture was cooled
  4. washwashed with ethyl acetate
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customPurification by column chromatography

Sources & evidence

ORD record
ord-158ca0bc81f541e7ba4172bd3a2521cf
Source dataset
uspto-grants-2000_10
Patent number
US06133255

Reaction notes

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