Phosgene → N-(5-Chloropyridin-2-yl)-2-[[1-(4-pyridinyl)pyrrolidin-3-yloxycarbonyl]amino]benzamide

HRID 988596

反応式

HRID 988596 の反応式
[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8]2)=[CH:3][CH:2]=1.CS(O)(=O)=O.N1C2C(=CC=CC=2)C=CC=1.[C:28](Cl)(Cl)=[O:29].[Cl:32][C:33]1[CH:34]=[CH:35][C:36]([NH:39][C:40](=[O:48])[C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2[NH2:47])=[N:37][CH:38]=1>ClCCl.C1(C)C=CC=CC=1>[Cl:32][C:33]1[CH:34]=[CH:35][C:36]([NH:39][C:40](=[O:48])[C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2[NH:47][C:28]([O:12][CH:9]2[CH2:10][CH2:11][N:7]([C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)[CH2:8]2)=[O:29])=[N:37][CH:38]=1

参加物

8

反応物 5

HCID 6371PhosgeneHCID 6395Methanesulfonic AcidHCID 7047Quinoline2 回HCID 219061981-(Pyridin-4-yl)pyrrolidin-3-olHCID 219063812-amino-N-(5-chloropyridin-2-yl)benzamide

生成物 1

HCID 21906357N-(5-Chloropyridin-2-yl)-2-[[1-(4-pyridinyl)pyrrolidin-3-yloxycarbonyl]amino]benzamide収率 32.8%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

To as solution of 1-(4-pyridinyl)-3-hydroxypyrrolidine (330 mg, 2.01 mmol) in dichloromethane (30 mL) was added methanesulfonic acid (0.15 mL, 2.31 mmol). After 15 seconds, quinoline (0.3 mL, 2.54 mmol) was added, immediately followed by a toluene solution of phosgene (0.65 mL, 1.25 mmol). After 5 minutes, the reaction was placed in an oil bath at 35° C. After 45 minutes, the reaction was cooled to room temperature. N-(5-Chloropyridin-2-yl)-2-aminobenzamide (498 mg, 2.01 mmol) was added, followed by quinoline (0.3 mL, 2.54 mmol). After stirring overnight, the reaction was diluted with dichloromethane (150 mL) and washed with saturated aqueous sodium carbonate (2×25 mL). The organic layer was concentrated in vacuo and purified by flash column chromatography (100% CH2Cl2 to 9% MeOH/CH2Cl2) and then by HPLC to give the title product (181 mg, 0.41 mmol, 21%).

後処理

  1. waitAfter 5 minutes
  2. customthe reaction was placed in an oil bath at 35° C
  3. waitAfter 45 minutes
  4. washwashed with saturated aqueous sodium carbonate (2×25 mL)
  5. concentrationThe organic layer was concentrated in vacuo
  6. custompurified by flash column chromatography (100% CH2Cl2 to 9% MeOH/CH2Cl2)

出典と根拠

ORDレコード
ord-57330204374a45c9a659e73a357b3a1b
出典データセット
uspto-grants-2003_10
特許番号
US06635657B1

関連ノート

読み込み中…