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

HRID 1970534Notes

Reaction equation

HRID 1970534 reaction equation
[CH:1]1([CH2:4][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]([OH:29])=O)[CH:17]=2)=[O:7])[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:64][C@H:65]([C:75]([O:77][CH3:78])=[O:76])[CH2:66][CH2:67][C:68](=[O:74])[O:69][C:70]([CH3:73])([CH3:72])[CH3:71].Cl>CN(C=O)C>[CH3:78][O:77][C:75](=[O:76])[C@@H:65]([NH:64][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][CH2:4][CH:1]2[CH2:2][CH2:3]2)=[O:30])[N:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:19]=1)=[O:29])[CH2:66][CH2:67][C:68]([O:69][C:70]([CH3:71])([CH3:72])[CH3:73])=[O:74]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 16218751L-Glutamic acid, 5-(1,1-dimethylethyl) 1-methyl ester, hydrochloride (1:1)HCID 668548665-[2-((S)-2-(Cyclopropylmethyl-carbamoyl)-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 66855322(S)-2-({5-[2-((S)-2-(Cyclopropylmethyl-carbamoyl)-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 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1.50 g 5-[2-((S)-2-(Cyclopropylmethyl-carbamoyl)-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid in 22 ml DMF were added 0.60 ml DIPEA, 1.38 g HATU and 923 mg 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 obtained after evaporation of the solvent was purified by chromatography on silica using DCM/MeOH 97:3 as eluent. Yield: 2.0 g.

Workup

  1. concentrationwas concentrated
  2. extractionsubsequently extracted with aqueous LiCl (4%), 0.1 M HCl and saturated NaHCO3

Sources & evidence

ORD record
ord-f0455a681e554613bac5619259f389bf
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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