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

HRID 1185453Notes

Reaction equation

HRID 1185453 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:43])[C@@H:13]([NH:23][C:24]([C:26]2[CH:35]=[C:34]([O:36][C@@H:37]([C:39]([OH:41])=O)[CH3:38])[C:33]3[C:28](=[CH:29][C:30]([CH3:42])=[CH:31][CH:32]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[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:67]1([NH:71][C:72]([C@@H:74]2[CH2:78][CH2:77][CH2:76][NH:75]2)=[O:73])[CH2:70][CH2:69][CH2:68]1>C(Cl)Cl.O>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:43])[C@@H:13]([NH:23][C:24]([C:26]2[CH:35]=[C:34]([O:36][C@H:37]([CH3:38])[C:39]([N:75]3[CH2:76][CH2:77][CH2:78][C@H:74]3[C:72](=[O:73])[NH:71][CH:67]3[CH2:68][CH2:69][CH2:70]3)=[O:41])[C:33]3[C:28](=[CH:29][C:30]([CH3:42])=[CH:31][CH:32]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 13041PentafluorophenolHCID 685972714-((S)-4-tert-Butoxycarbonyl-2-{[4-((R)-1-carboxy-ethoxy)-7-methyl-quinoline-2-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl esterHCID 68599196(S)-Pyrrolidine-2-carboxylic acid cyclobutylamide trifluoroacetate

Product 1

HCID 686019374-[(S)-4-tert-Butoxycarbonyl-2-({4-[(R)-2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-1-methyl-2-oxo-ethoxy]-7-methyl-quinoline-2-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 250 mg of 4-((S)-4-tert-Butoxycarbonyl-2-{[4-((R)-1-carboxy-ethoxy)-7-methyl-quinoline-2-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl ester in 2.5 ml of DCM, 96 mg of EDC, 92 mg of pentafluorophenol was added and the reaction mixture was stirred for 2 h. Then, 117 mg of (S)-Pyrrolidine-2-carboxylic acid cyclobutylamide trifluoroacetate and 192 mg of NEM in 2 ml of DCM was added. After 2 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-36afdfcc0d8445e1948b3e3fffda0fef
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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