(R)-Quinuclidin-3-yl 2-hydroxy-2,2-di(thiophen-2-yl)acetate → (R)-3-(2-Hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-(pyrimidin-4-ylcarbamoylmethyl)-1-azonia-bicyclo[2.2.2]octane bromide

HRID 1920569ノート

反応式

HRID 1920569 の反応式
[Br:1][CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][N:9]=[CH:8][N:7]=1)=[O:4].[N:12]12[CH2:19][CH2:18][CH:15]([CH2:16][CH2:17]1)[C@@H:14]([O:20][C:21](=[O:34])[C:22]([OH:33])([C:28]1[S:29][CH:30]=[CH:31][CH:32]=1)[C:23]1[S:24][CH:25]=[CH:26][CH:27]=1)[CH2:13]2>C(Cl)(Cl)Cl.C(#N)C>[Br-:1].[OH:33][C:22]([C:23]1[S:24][CH:25]=[CH:26][CH:27]=1)([C:28]1[S:29][CH:30]=[CH:31][CH:32]=1)[C:21]([O:20][C@@H:14]1[CH:15]2[CH2:18][CH2:19][N+:12]([CH2:2][C:3](=[O:4])[NH:5][C:6]3[CH:11]=[CH:10][N:9]=[CH:8][N:7]=3)([CH2:17][CH2:16]2)[CH2:13]1)=[O:34]

参加物

4

反応物 2

HCID 44232927(R)-Quinuclidin-3-yl 2-hydroxy-2,2-di(thiophen-2-yl)acetateHCID 445419272-Bromo-N-pyrimidin-4-yl-acetamide

生成物 1

HCID 86611384(R)-3-(2-Hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-(pyrimidin-4-ylcarbamoylmethyl)-1-azonia-bicyclo[2.2.2]octane bromide

試薬・触媒・溶媒 1

HCID 22555007Acetonitrile chloroform溶媒

実験手順

A solution of 2-Bromo-N-pyrimidin-4-yl-acetamide (0.90 g, 4.17 mmol) and hydroxy-di-thiophen-2-yl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl) ester (Example 70(ii)) (1.32 g, 3.79 mmol) in dry chloroform-acetonitrile (20 ml+4 ml) are heated at 50° C. for 3 hours. The mixture is then cooled to room temperature and concentrated. Purification by reverse phase C18 column chromatography (gradient elution 100% water to 100% acetonitrile) gives after concentration a light brown solid. The solid was triturated with hot acetonitrile then dissolved in hot acetonitrile containing a few drops of water. After standing at 5° C. for several hours crystals are formed which are filtered and dried to give the title compound.

後処理

  1. concentrationconcentrated
  2. customPurification
  3. washby reverse phase C18 column chromatography (gradient elution 100% water to 100% acetonitrile)
  4. customgives
  5. concentrationafter concentration a light brown solid
  6. customThe solid was triturated with hot acetonitrile
  7. dissolutionthen dissolved in hot acetonitrile containing a few drops of water
  8. waitAfter standing at 5° C. for several hours
  9. customcrystals are formed which
  10. filtrationare filtered
  11. customdried

出典と根拠

ORDレコード
ord-00d1a659282244e481c0f059ceed3b18
出典データセット
uspto-grants-2012_05
特許番号
US08168654B2

反応ノート

読み込み中…