1,2-Dichloroethane → 4-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-4-methoxycarbonyl-butyryl]-piperazine-1-carboxylic acid propyl ester

HRID 1970599Notes

Reaction equation

HRID 1970599 reaction equation
[CH2:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13](=[O:50])[C@@H:14]([NH:20][C:21]([C:23]2[CH:27]=[C:26]([O:28][CH2:29][C:30]([N:32]3[CH2:36][CH2:35][CH2:34][C@H:33]3[C:37](=[O:43])[NH:38][CH:39]3[CH2:42][CH2:41][CH2:40]3)=[O:31])[N:25]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[N:24]=2)=[O:22])[CH2:15][CH2:16][C:17]([OH:19])=[O:18])[CH2:9][CH2:8]1)=[O:6])[CH2:2][CH3:3].[CH2:51](Cl)CCl.CO>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH2:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13](=[O:50])[C@@H:14]([NH:20][C:21]([C:23]2[CH:27]=[C:26]([O:28][CH2:29][C:30]([N:32]3[CH2:36][CH2:35][CH2:34][C@H:33]3[C:37](=[O:43])[NH:38][CH:39]3[CH2:40][CH2:41][CH2:42]3)=[O:31])[N:25]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[N:24]=2)=[O:22])[CH2:15][CH2:16][C:17]([O:19][CH3:51])=[O:18])[CH2:9][CH2:8]1)=[O:6])[CH2:2][CH3:3]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 887MethanolHCID 668557324-[(S)-4-Carboxy-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid propyl ester

Product 1

HCID 441295274-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-4-methoxycarbonyl-butyryl]-piperazine-1-carboxylic acid propyl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 150 mg 4-[(S)-4-Carboxy-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid propyl ester in 3 ml DMF were added 42 mg EDC, 27 mg DMAP and 37 μl methanol. After 3 h the reaction mixture was concentrated and the residue purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were lyophilized to yield the pure product. Yield: 40 mg MS (ES+): m/e=710.

Workup

  1. concentrationAfter 3 h the reaction mixture was concentrated
  2. customthe residue purified by preparative HPLC (
  3. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  4. additionThe fractions containing the product
  5. customto yield the pure product

Sources & evidence

ORD record
ord-4afa6efc785a411c88762ee0f12014cc
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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