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 butyl ester

HRID 1970600Notes

Reaction equation

HRID 1970600 reaction equation
[CH2:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:51])[C@@H:15]([NH:21][C:22]([C:24]2[CH:28]=[C:27]([O:29][CH2:30][C:31]([N:33]3[CH2:37][CH2:36][CH2:35][C@H:34]3[C:38](=[O:44])[NH:39][CH:40]3[CH2:43][CH2:42][CH2:41]3)=[O:32])[N:26]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[N:25]=2)=[O:23])[CH2:16][CH2:17][C:18]([OH:20])=[O:19])[CH2:10][CH2:9]1)=[O:7])[CH2:2][CH2:3][CH3:4].[CH2:52](Cl)CCl.CO>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH2:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:51])[C@@H:15]([NH:21][C:22]([C:24]2[CH:28]=[C:27]([O:29][CH2:30][C:31]([N:33]3[CH2:37][CH2:36][CH2:35][C@H:34]3[C:38](=[O:44])[NH:39][CH:40]3[CH2:43][CH2:42][CH2:41]3)=[O:32])[N:26]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[N:25]=2)=[O:23])[CH2:16][CH2:17][C:18]([O:20][CH3:52])=[O:19])[CH2:10][CH2:9]1)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 887MethanolHCID 441290604-[(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 butyl ester

Product 1

HCID 668568564-[(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 butyl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 120 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 butyl ester in 3 ml DMF were added 39 mg EDC, 25 mg DMAP and 34 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: 47 mg MS (ES+): m/e=724.

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-5e01aca2c37e4c9fb2a5157f59f43f68
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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