1,2-Dichloroethane → 4-[(S)-3-tert-Butoxycarbonyl-2-({4-[(R)-2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-1-methyl-2-oxo-ethoxy]-7-methyl-quinoline-2-carbonyl}-amino)-propionyl]-piperazine-1-carboxylic acid ethyl ester

HRID 1185450Notes

Reaction equation

HRID 1185450 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:42])[C@@H:13]([NH:22][C:23]([C:25]2[CH:34]=[C:33]([O:35][C@@H:36]([C:38]([OH:40])=O)[CH3:37])[C:32]3[C:27](=[CH:28][C:29]([CH3:41])=[CH:30][CH:31]=3)[N:26]=2)=[O:24])[CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:8][CH2:7]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:66]1([NH:70][C:71]([C@@H:73]2[CH2:77][CH2:76][CH2:75][NH:74]2)=[O:72])[CH2:69][CH2:68][CH2:67]1>C(Cl)Cl.O>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:42])[C@@H:13]([NH:22][C:23]([C:25]2[CH:34]=[C:33]([O:35][C@H:36]([CH3:37])[C:38]([N:74]3[CH2:75][CH2:76][CH2:77][C@H:73]3[C:71](=[O:72])[NH:70][CH:66]3[CH2:67][CH2:68][CH2:69]3)=[O:40])[C:32]3[C:27](=[CH:28][C:29]([CH3:41])=[CH:30][CH:31]=3)[N:26]=2)=[O:24])[CH2:14][C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 13041PentafluorophenolHCID 68599196(S)-Pyrrolidine-2-carboxylic acid cyclobutylamide trifluoroacetateHCID 685999614-((S)-3-tert-Butoxycarbonyl-2-{[4-((R)-1-carboxy-ethoxy)-7-methyl-quinoline-2-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid ethyl ester

Product 1

HCID 685988074-[(S)-3-tert-Butoxycarbonyl-2-({4-[(R)-2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-1-methyl-2-oxo-ethoxy]-7-methyl-quinoline-2-carbonyl}-amino)-propionyl]-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 121 mg of 4-((S)-3-tert-Butoxycarbonyl-2-{[4-((R)-1-carboxy-ethoxy)-7-methyl-quinoline-2-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid ethyl ester in 1 ml of DCM, 43 mg of EDC, 43 mg of pentafluorophenol and 27 mg of NEM was added and the reaction mixture was stirred for 2 h. Then, 67 mg of (S)-Pyrrolidine-2-carboxylic acid cyclobutylamide trifluoroacetate and 20 mg of NEM in 2 ml of DCM was added. After 1 h the reaction mixture was diluted with water. After filtration through a chem Elut® cartridge by eluting with ethyl acetate the solvents were removed under reduced pressure. The isolated crude product was pure enough for the next reaction step.

Workup

  1. filtrationAfter filtration through a chem Elut® cartridge
  2. washby eluting with ethyl acetate the solvents
  3. customwere removed under reduced pressure
  4. customThe isolated crude product
  5. customwas pure enough for the next reaction step

Sources & evidence

ORD record
ord-3e6b061222f444cc99319a868cc39e28
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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