1-Hydroxybenzotriazole → 5-[2-((S)-2-Benzyloxycarbonyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid ethyl ester

HRID 1970453Notes

Reaction equation

HRID 1970453 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([O:11][CH2:12][C:13]([OH:15])=O)[N:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:7]=1)=[O:5])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[CH2:42]([O:49][C:50](=[O:56])[C@@H:51]1[CH2:55][CH2:54][CH2:53][NH:52]1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>CN(C=O)C.C(Cl)CCl>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([O:11][CH2:12][C:13]([N:52]2[CH2:53][CH2:54][CH2:55][C@H:51]2[C:50]([O:49][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:56])=[O:15])[N:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:7]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733413Proline benzyl ester hydrochlorideHCID 668550565-Carboxymethoxy-1-phenyl-1H-pyrazole-3-carboxylic acid ethyl ester

Product 1

HCID 668549795-[2-((S)-2-Benzyloxycarbonyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 9.5 g 5-carboxymethoxy-1-phenyl-1H-pyrazole-3-carboxylic acid ethyl ester in 100 ml DMF were added 5.0 g HOBt, 6.3 g EDC and 10.9 ml DIPEA. After 5 minutes 7.9 g L-proline benzyl ester hydrochloride were added and the resulting solution stirred for 16 h. The reaction mixture was concentrated, dissolved in dichloromethane and extracted with aqueous LiCl (4%) and saturated NaHCO3. The crude product obtained after evaporation of the solvent was purified by flash chromatography on silica using ethyl acetate/heptane 1:1 as eluent. Yield: 13.2 g colorless foam.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutiondissolved in dichloromethane
  3. extractionextracted with aqueous LiCl (4%) and saturated NaHCO3

Sources & evidence

ORD record
ord-405d8196d33c42b3a076a1a7251815f5
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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