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

HRID 1185515Notes

Reaction equation

HRID 1185515 reaction equation
[C:1]([C@H:4]([O:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([CH3:17])=[CH:14][CH:15]=2)[N:10]=[C:9]([C:18]([OH:20])=[O:19])[CH:8]=1)[CH3:5])([OH:3])=O.F[C:22]1C(O)=C(F)C(F)=C(F)C=1F.Cl.[CH:34]1([NH:38][C:39]([C@@H:41]2[CH2:45][CH2:44][CH2:43][NH:42]2)=[O:40])[CH2:37][CH2:36][CH2:35]1.C(N1CCOCC1)C>C(Cl)Cl.O.C(Cl)CCl>[CH3:22][O:20][C:18]([C:9]1[CH:8]=[C:7]([O:6][C@H:4]([CH3:5])[C:1]([N:42]2[CH2:43][CH2:44][CH2:45][C@H:41]2[C:39](=[O:40])[NH:38][CH:34]2[CH2:37][CH2:36][CH2:35]2)=[O:3])[C:16]2[C:11](=[CH:12][C:13]([CH3:17])=[CH:14][CH:15]=2)[N:10]=1)=[O:19]

Participants

8

Reactant 4

HCID 7525EthylmorpholineHCID 13041PentafluorophenolHCID 68597555(S)-Pyrrolidine-2-carboxylic acid cyclobutylamide hydrochlorideHCID 68598842HCID 68598842, compound

Product 1

HCID 686020364-[(R)-2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-1-methyl-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1.30 g 4-((R)-1-Carboxy-ethoxy)-7-methyl-quinoline-2-carboxylic acid in 10 ml DCM, 1.24 g pentafluorophenol and 1.29 g EDC were added. The mixture was stirred under exclusion of moisture until LCMS indicated complete conversion to the corresponding pentafluorophenolester. (S)-Pyrrolidine-2-carboxylic acid cyclobutylamide hydrochloride (1.10 g) was mixed with 1.1 ml N-ethylmorpholine and 5 ml DCM and this mixture added dropwise to the solution of the pentafluorophenolester. After 12 h the reaction mixture was diluted with water and extracted with DCM. The crude product obtained after evaporation of the solvent was purified by flash chromatography on silica eluting with ethyl acetate/heptane gradient. Yield: 1.40 g.

Workup

  1. additionthis mixture added dropwise to the solution of the pentafluorophenolester
  2. extractionextracted with DCM

Sources & evidence

ORD record
ord-0edff2d9768c43fa97950788d4b50a9f
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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