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

HRID 988596

Reaction equation

HRID 988596 reaction equation
[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

Participants

8

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-57330204374a45c9a659e73a357b3a1b
Source dataset
uspto-grants-2003_10
Patent number
US06635657B1

Linked notes

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