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

HRID 8618Notes

Reaction equation

HRID 8618 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:13]=[CH:12][C:7]([O:8][CH2:9][CH2:10][OH:11])=[CH:6][CH:5]=1.Cl[C:15]1[N:20]=[CH:19][N:18]=[C:17]([NH:21][S:22]([CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)(=[O:24])=[O:23])[C:16]=1[C:33]1[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=1>COCCOC>[Br:3][C:4]1[CH:13]=[CH:12][C:7]([O:8][CH2:9][CH2:10][O:11][C:15]2[N:20]=[CH:19][N:18]=[C:17]([NH:21][S:22]([CH2:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)(=[O:23])=[O:24])[C:16]=2[C:33]2[CH:34]=[CH:35][C:36]([CH3:39])=[CH:37][CH:38]=2)=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 991682-(p-Bromophenoxy)ethanolHCID 865924692-Phenyl-ethanesulfonic acid (6-chloro-5-p-tolyl-pyrimidin-4-yl)-amide

Product 1

HCID 235482522-Phenyl-ethanesulfonic acid {6-[2-(4-bromo-phenoxy)-ethoxy]-5-p-tolyl-pyrimidin-4-yl}-amideYield 86.7%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
70 °C

Procedure

To a suspension of NaH (17 mg, 60% in mineral oil) in DME (5 ml) was added 2-(4-bromo-phenoxy)-ethanol (111 mg). The mixture was stirred at 50° C. for 1 h before 2-phenyl-ethanesulfonic acid (6-chloro-5-p-tolyl-pyrimidin-4-yl)-amide (100 mg, Referential Example 1f) and K-tert.-butylate (25 mg) was added. The mixture was stirred at 70° C. for 16 h. A further portion of K-tert.-butylate (50 mg) was added and stirring was continued at 70° C. for 12 h and at rt for 72 h. The solvent was evaporated. The residue was treated with water (40 ml), acidified with 10% aq. citric acid and extracted twice with EA (50 ml). The organic phase was washed with water and evaporated. The crude product was crystallised from 2-propanol to give 2-phenyl-ethanesulfonic acid {6-[2-(4-bromo-phenoxy)-ethoxy]-5-p-tolyl-pyrimidin-4-yl}-amide (127 mg) as a beige powder. LC-MS: tR=6.14 min, [M+1]+=568.38, [M−1]−=570.15.

Workup

  1. additionwas added
  2. stirringstirring
  3. waitwas continued at 70° C. for 12 h and at rt for 72 h
  4. customThe solvent was evaporated
  5. additionThe residue was treated with water (40 ml)
  6. extractionextracted twice with EA (50 ml)
  7. washThe organic phase was washed with water
  8. customevaporated
  9. customThe crude product was crystallised from 2-propanol

Sources & evidence

ORD record
ord-f82597da22f34e6c9d823c81ffb52c3e
Source dataset
uspto-grants-2006_08
Patent number
US07091201B2

Reaction notes

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