Sodium hydride → N-[6-[2-(5-Bromo-pyrimidin-2-yloxy)-ethoxy]-5-(3-methoxy-phenoxy)-pyrimidin-4-yl]-4-tert-butyl-benzenesulfonamide

HRID 1082264

Reaction equation

HRID 1082264 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=3)=[C:19]([O:30][CH2:31][CH2:32][OH:33])[N:18]=[CH:17][N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Br:36][C:37]1[CH:38]=[N:39][C:40](Cl)=[N:41][CH:42]=1.[Cl-].[NH4+]>CC(N(C)C)=O>[Br:36][C:37]1[CH:38]=[N:39][C:40]([O:33][CH2:32][CH2:31][O:30][C:19]2[N:18]=[CH:17][N:16]=[C:15]([NH:14][S:11]([C:8]3[CH:9]=[CH:10][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:6][CH:7]=3)(=[O:12])=[O:13])[C:20]=2[O:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=2)=[N:41][CH:42]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 122044Ro 46-2005HCID 6066655-Bromo-2-chloropyrimidine

Product 1

HCID 11006709N-[6-[2-(5-Bromo-pyrimidin-2-yloxy)-ethoxy]-5-(3-methoxy-phenoxy)-pyrimidin-4-yl]-4-tert-butyl-benzenesulfonamideYield 84.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of 4-tert-butyl-N-{6-(2-hydroxyethoxy)-5-(3-methoxyphenoxy)pyrimidin-4-yl}benzenesulfonamide (250 mg) in dimethylacetamide (5 ml) is added sodium hydride (60% dispersion-type, 64 mg) at room temperature, and the mixture is stirred for 20 minutes. To the reaction solution is added 5-bromo-2-chloropyrimidine (133 mg), and the mixture is stirred at room temperature for 18 hours. The reaction solution is poured into ice-water, and the mixture is neutralized with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The ethyl acetate layer is washed, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; chloroform/methanol=40:1) to give crude crystals, which are recrystallized from ethyl acetate/diisopropyl ether to give N-[-6-{2-(5-bromopyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide (280 mg) as crystals.

Workup

  1. stirringthe mixture is stirred at room temperature for 18 hours
  2. extractionextracted with ethyl acetate
  3. washThe ethyl acetate layer is washed
  4. customdried
  5. customevaporated
  6. customto remove the solvent
  7. customThe residue is purified by silica gel column chromatography (solvent; chloroform/methanol=40:1)
  8. customto give crude crystals, which
  9. customare recrystallized from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-a2dd41097b35423ab56dad8736e9691d
Source dataset
uspto-grants-1996_12
Patent number
US05589478

Linked notes

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