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

HRID 1247027

Reaktionsgleichung

Reaktionsgleichung von HRID 1247027
[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 reaction was cooled to room temperature. N-(5-Chloropyridin-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-48f404344ede43d0912950d1ec2ce80a
Quelldatensatz
uspto-grants-2006_10
Patentnummer
US07129245B2

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