Ethylmorpholine → 4-[2-((S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid methyl ester

HRID 1185585Notes

Reaction equation

HRID 1185585 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:14]=[C:13]([O:15][CH2:16][C:17]([OH:19])=O)[C:12]2[C:7](=[CH:8][C:9]([CH3:20])=[CH:10][CH:11]=2)[N:6]=1)=[O:4].FC1C(O)=C(F)C(F)=C(F)C=1F.Cl.[C:34]([C@@H:36]1[CH2:40][CH2:39][CH2:38][NH:37]1)#[N:35].C(N1CCOCC1)C>CN(C=O)C.C(Cl)Cl.C(Cl)CCl>[CH3:1][O:2][C:3]([C:5]1[CH:14]=[C:13]([O:15][CH2:16][C:17]([N:37]2[CH2:38][CH2:39][CH2:40][C@H:36]2[C:34]#[N:35])=[O:19])[C:12]2[C:7](=[CH:8][C:9]([CH3:20])=[CH:10][CH:11]=2)[N:6]=1)=[O:4]

Participants

8

Reactant 4

HCID 7525EthylmorpholineHCID 13041PentafluorophenolHCID 44593801(2S)-Pyrrolidine-2-carbonitrile hydrochlorideHCID 685989324-Carboxymethoxy-7-methyl-quinoline-2-carboxylic acid methyl ester

Product 1

HCID 686009994-[2-((S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1000 mg 4-Carboxymethoxy-7-methyl-quinoline-2-carboxylic acid methyl ester in 5 ml DMF were added 956 mg pentafluorophenol and 994 mg EDC. The mixture was stirred under exclusion of moisture until LCMS indicated complete conversion to the corresponding pentafluorophenolester. (S)-2-Cyano-pyrrolidine hydrochloride (437 mg) was mixed with 1.3 ml N-ethylmorpholine and 10 ml DMF and this mixture added dropwise to the solution of the pentafluorophenolester. After 12 h the reaction mixture was diluted with DCM and washed with aqueous LiCl (4%) and saturated aqueous NaHCO3. The crude product obtained after evaporation of the solvent was purified by flash chromatography on silica eluting with ethyl acetate/heptane gradient. Yield: 772 mg.

Workup

  1. additionthis mixture added dropwise to the solution of the pentafluorophenolester
  2. washwashed with aqueous LiCl (4%) and saturated aqueous NaHCO3

Sources & evidence

ORD record
ord-0bbc084fdf27409b834ee36d337187a2
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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