Sodium hydride → 6-[2-(5-Bromopyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-amine

HRID 1082302Notes

Reaction equation

HRID 1082302 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][CH2:9][CH2:10][OH:11])[C:3]=1[C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=1.[H-].[Na+].[Br:21][C:22]1[CH:23]=[N:24][C:25](Cl)=[N:26][CH:27]=1.[Cl-].[NH4+]>O1CCCC1>[Br:21][C:22]1[CH:23]=[N:24][C:25]([O:11][CH2:10][CH2:9][O:8][C:4]2[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=2[C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)=[N:26][CH:27]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 6066655-Bromo-2-chloropyrimidineHCID 111182972-{6-Amino-5-(4-methylphenyl)-pyrimidin-4-yloxy}ethanol

Product 1

HCID 117291026-[2-(5-Bromopyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-amineYield 91.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-{6-amino-5-(4-methylphenyl)pyrimidin-4-yloxy}ethanol (7.54 g) in tetrahydrofuran (150 ml) is added sodium hydride (60% dispersion-type, 1.47 g), and thereto is added 5-bromo-2-chloropyrimidine (7.73 g), and the mixture is stirred at room temperature overnight. To the reaction solution is added saturated aqueous ammonium chloride solution, and the mixture is evaporated to remove the solvent. The precipitated crystals are collected by filtration, washed and dried. The crude crystals are purified by silica gel column chromatography (solvent; chloroform/methanol=100:1~80:1), and recrystallized from tetrahydrofuran/diethyl ether to give 6-[2-(5-bromopyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-amine (11.27 g).

Workup

  1. customthe mixture is evaporated
  2. customto remove the solvent
  3. filtrationThe precipitated crystals are collected by filtration
  4. washwashed
  5. customdried
  6. customThe crude crystals are purified by silica gel column chromatography (solvent; chloroform/methanol=100:1~80:1)
  7. customrecrystallized from tetrahydrofuran/diethyl ether

Sources & evidence

ORD record
ord-95e140930bd44191b32fb1429bf715bb
Source dataset
uspto-grants-1996_12
Patent number
US05589478

Reaction notes

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