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

HRID 1882925

Reaktionsgleichung

Reaktionsgleichung von HRID 1882925
[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

Komponenten

8

Edukt 5

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

Produkt 1

HCID 21906357N-(5-Chloropyridin-2-yl)-2-[[1-(4-pyridinyl)pyrrolidin-3-yloxycarbonyl]amino]benzamideAusbeute 32,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

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 r action was cooled to room temperature. N-(5-Chloro-pyridin-2-yl)-2-aminobenzamide (498 mg, 2.01 mmol) was added, followed by quinolin (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%).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-c9daee0915b54de680f8ee8a672f60d7
Quelldatensatz
uspto-grants-2004_07
Patentnummer
US06759414B2

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