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

HRID 1185508Notes

Reaction equation

HRID 1185508 reaction equation
[CH2:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:44])[C@@H:15]([NH:25][C:26]([C:28]2[CH:37]=[C:36]([O:38][CH2:39][C:40]([OH:42])=O)[C:35]3[C:30](=[CH:31][C:32]([CH3:43])=[CH:33][CH:34]=3)[CH:29]=2)=[O:27])[CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:10][CH2:9]1)=[O:7])[CH2:2][CH2:3][CH3:4].C(Cl)CCl.FC1C(O)=C(F)C(F)=C(F)C=1F.Cl.[CH:62]1([NH:66][C:67]([C@@H:69]2[CH2:73][CH2:72][CH2:71][NH:70]2)=[O:68])[CH2:65][CH2:64][CH2:63]1>C(Cl)Cl.O>[CH2:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14](=[O:44])[C@@H:15]([NH:25][C:26]([C:28]2[CH:37]=[C:36]([O:38][CH2:39][C:40]([N:70]3[CH2:71][CH2:72][CH2:73][C@H:69]3[C:67](=[O:68])[NH:66][CH:62]3[CH2:63][CH2:64][CH2:65]3)=[O:42])[C:35]3[C:30](=[CH:31][C:32]([CH3:43])=[CH:33][CH:34]=3)[CH:29]=2)=[O:27])[CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[CH2:12][CH2:13]1)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 13041PentafluorophenolHCID 68597555(S)-Pyrrolidine-2-carboxylic acid cyclobutylamide hydrochlorideHCID 685984354-{(S)-4-tert-Butoxycarbonyl-2-[(4-carboxymethoxy-7-methyl-naphthalene-2-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid butyl ester

Product 1

HCID 685969714-[(S)-4-tert-Butoxycarbonyl-2-({4-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-naphthalene-2-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 670 mg of 4-{(S)-4-tert-Butoxycarbonyl-2-[(4-carboxymethoxy-7-methyl-naphthalene-2-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid butyl ester in 10 ml of DCM, 418 mg of EDC, 402 mg of pentafluorophenol was added and the reaction mixture was stirred for 2 h. Then, 329 mg of (S)-Pyrrolidine-2-carboxylic acid cyclobutylamide hydrochloride and 251 mg of NEM in 1.5 ml of DCM was added. After 16 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 crude product obtained after evaporation of the solvent was purified by flash chromatography on silica using an ethyl acetate/heptane gradient. Yield: 1.5 g

Workup

  1. filtrationAfter filtration through a chem Elut® cartridge
  2. washby eluting with ethyl acetate the solvents
  3. customwere removed under reduced pressure

Sources & evidence

ORD record
ord-eabb84e43e9a472fa0113e12a71357d4
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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