Sodium hydride → 2-Phenyl-ethenesulfonic acid {6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-p-tolyl-pyrimidin-4-yl}-amide

HRID 965629Notes

Reaction equation

HRID 965629 reaction equation
[H-].[Na+].[OH:3][CH2:4][CH2:5][O:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]([NH:13][S:14]([CH:17]=[CH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:16])=[O:15])[C:8]=1[C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=1.[Br:32][C:33]1[CH:34]=[N:35][C:36](Cl)=[N:37][CH:38]=1>C1COCC1>[Br:32][C:33]1[CH:34]=[N:35][C:36]([O:3][CH2:4][CH2:5][O:6][C:7]2[N:12]=[CH:11][N:10]=[C:9]([NH:13][S:14]([CH:17]=[CH:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)(=[O:15])=[O:16])[C:8]=2[C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=2)=[N:37][CH:38]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 6066655-Bromo-2-chloropyrimidineHCID 695584832-Phenyl-ethenesulfonic acid [6-(2-hydroxy-ethoxy)-5-p-tolyl-pyrimidin-4-yl]-amide

Product 1

HCID 695583782-Phenyl-ethenesulfonic acid {6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-p-tolyl-pyrimidin-4-yl}-amideYield 26.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To sodium hydride (220 mg, 55-65% in mineral oil) was added THF (35 ml) followed by addition of 2-phenyl-ethenesulfonic acid [6-(2-hydroxy-ethoxy)-5-p-tolyl-pyrimidin-4-yl]-amide (250 mg). The mixture was stirred for 1 h at rt. Then 5-bromo-2-chloro-pyrimidine (188 mg) was added and stirring continued for 21 h at 80° C. The solvent was evaporated and diethylether (20 ml) was added to the residue. The precipitate was filtered off and washed with diethylether, dissolved in water and acidified by citric acid. The precipitate was filtered off and the crude material was purified by chromatography over silicagel with hexane/EtOAc=1/1 to give 2-phenyl-ethenesulfonic acid {6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-5-p-tolyl-pyrimidin-4-yl}-amide (91 mg); tR=5.39 (LC); [M+H]+=570.34 (ES+); [M−H]−=568.45 (ES−).

Workup

  1. stirringstirring
  2. waitcontinued for 21 h at 80° C
  3. customThe solvent was evaporated
  4. additiondiethylether (20 ml) was added to the residue
  5. filtrationThe precipitate was filtered off
  6. washwashed with diethylether
  7. dissolutiondissolved in water
  8. filtrationThe precipitate was filtered off
  9. customthe crude material was purified by chromatography over silicagel with hexane/EtOAc=1/1

Sources & evidence

ORD record
ord-d2fdf62fda004e5bbcd45efc995e12b6
Source dataset
uspto-grants-2005_10
Patent number
US06951856B2

Reaction notes

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