1,2-Dichloroethane → 4-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid ethyl ester

HRID 1185462Notes

Reaction equation

HRID 1185462 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:15]=[C:14]([O:16][CH2:17][C:18]([OH:20])=O)[C:13]2[C:8](=[CH:9][C:10]([CH3:21])=[CH:11][CH:12]=2)[N:7]=1)=[O:5])[CH3:2].C(Cl)CCl.FC1C(O)=C(F)C(F)=C(F)C=1F.FC(F)(F)C(O)=O.[CH:45]1([NH:49][C:50]([C@@H:52]2[CH2:56][CH2:55][CH2:54][NH:53]2)=[O:51])[CH2:48][CH2:47][CH2:46]1>C(Cl)Cl.O>[CH2:1]([O:3][C:4]([C:6]1[CH:15]=[C:14]([O:16][CH2:17][C:18]([N:53]2[CH2:54][CH2:55][CH2:56][C@H:52]2[C:50](=[O:51])[NH:49][CH:45]2[CH2:46][CH2:47][CH2:48]2)=[O:20])[C:13]2[C:8](=[CH:9][C:10]([CH3:21])=[CH:11][CH:12]=2)[N:7]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 13041PentafluorophenolHCID 68599196(S)-Pyrrolidine-2-carboxylic acid cyclobutylamide trifluoroacetateHCID 686015834-Carboxymethoxy-7-methyl-quinoline-2-carboxylic acid ethyl ester

Product 1

HCID 685994424-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2 g of 4-Carboxymethoxy-7-methyl-quinoline-2-carboxylic acid ethyl ester in 30 ml of DCM, 3.6 g of EDC, 3.4 g of pentafluorophenol, 2.2 g of NEM was added and the reaction mixture was stirred at RT for 2 h. Then, 5.3 g of (S)-Pyrrolidine-2-carboxylic acid cyclobutylamide trifluoroacetate and 2.1 g of NEM in 10 ml of DCM was added. After 16 h the reaction mixture was diluted with water and extracted with DCM (3×150 ml). The combined organic phases were dried over MgSO4 and the solvents were removed under reduced pressure. The crude product was purified by chromatography on silica gel eluting with a gradient of n-heptane/ethyl acetate. The fractions containing the product were combined and the solvent evaporated under reduced pressure. Yield: 2.5 g.

Workup

  1. extractionextracted with DCM (3×150 ml)
  2. dry with materialThe combined organic phases were dried over MgSO4
  3. customthe solvents were removed under reduced pressure
  4. customThe crude product was purified by chromatography on silica gel eluting with a gradient of n-heptane/ethyl acetate
  5. additionThe fractions containing the product
  6. customthe solvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-9f43992f43324901ae72d827f35fcea8
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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