1-Hydroxybenzotriazole → (S)-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-pentanedioic acid 5-tert-butyl ester 1-methyl ester

HRID 1970467Notes

Reaction equation

HRID 1970467 reaction equation
[CH:1]1([NH:5][C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13](=[O:30])[CH2:14][O:15][C:16]2[N:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:19]=[C:18]([C:27](O)=[O:28])[CH:17]=2)=[O:7])[CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.[NH2:50][C@H:51]([C:61]([O:63][CH3:64])=[O:62])[CH2:52][CH2:53][C:54](=[O:60])[O:55][C:56]([CH3:59])([CH3:58])[CH3:57].Cl>CN(C=O)C.C(Cl)CCl>[CH3:64][O:63][C:61](=[O:62])[C@@H:51]([NH:50][C:27]([C:18]1[CH:17]=[C:16]([O:15][CH2:14][C:13]([N:9]2[CH2:10][CH2:11][CH2:12][C@H:8]2[C:6](=[O:7])[NH:5][CH:1]2[CH2:2][CH2:3][CH2:4]2)=[O:30])[N:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:19]=1)=[O:28])[CH2:52][CH2:53][C:54]([O:55][C:56]([CH3:57])([CH3:58])[CH3:59])=[O:60]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 16218751L-Glutamic acid, 5-(1,1-dimethylethyl) 1-methyl ester, hydrochloride (1:1)HCID 668546955-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 66854877(S)-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-pentanedioic acid 5-tert-butyl ester 1-methyl ester

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1.1 g 5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid in 20 ml DMF were added 1 ml DIPEA, 0.41 g HOBt, 0.51 g EDC and 0.68 g H-Glu(OtBu)-OMe hydrochloride. After stirring for 24 h the solution was concentrated, taken up with dichloromethane and subsequently extracted with aqueous LiCl (4%), 0.1 M HCl and saturated NaHCO3. The crude product was purified by flash chromatography on silica using an ethyl acetate/heptane 50:50 to 100:0 gradient.

Workup

  1. concentrationwas concentrated
  2. extractionsubsequently extracted with aqueous LiCl (4%), 0.1 M HCl and saturated NaHCO3
  3. customThe crude product was purified by flash chromatography on silica using an ethyl acetate/heptane 50:50 to 100:0 gradient

Sources & evidence

ORD record
ord-f3d54bdb2cbe481a8a1d30bab42682d1
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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