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

HRID 8618ノート

反応式

HRID 8618 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
70 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-f82597da22f34e6c9d823c81ffb52c3e
出典データセット
uspto-grants-2006_08
特許番号
US07091201B2

反応ノート

読み込み中…