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

HRID 1970529Notes

Reaction equation

HRID 1970529 reaction equation
[F:1][CH2:2][CH2:3][NH:4][C:5]([C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:29])[CH2:13][O:14][C:15]1[N:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:18]=[C:17]([C:26](O)=[O:27])[CH:16]=1)=[O:6].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.[NH2:63][C@H:64]([C:74]([O:76][CH3:77])=[O:75])[CH2:65][CH2:66][C:67](=[O:73])[O:68][C:69]([CH3:72])([CH3:71])[CH3:70].Cl>CN(C=O)C>[CH3:77][O:76][C:74](=[O:75])[C@@H:64]([NH:63][C:26]([C:17]1[CH:16]=[C:15]([O:14][CH2:13][C:12]([N:8]2[CH2:9][CH2:10][CH2:11][C@H:7]2[C:5](=[O:6])[NH:4][CH2:3][CH2:2][F:1])=[O:29])[N:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:18]=1)=[O:27])[CH2:65][CH2:66][C:67]([O:68][C:69]([CH3:71])([CH3:72])[CH3:70])=[O:73]

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 866504765-[2-((S)-2-(2-Fluoro-ethylcarbamoyl)-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 86650478(S)-2-({5-[2-((S)-2-(2-Fluoro-ethylcarbamoyl)-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 950 mg 5-[2-((S)-2-(2-Fluoro-ethylcarbamoyl)-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid in 15 ml DMF were added 0.39 ml DIPEA, 893 mg HATU and 596 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 used in the subsequent reaction. Yield: 1.3 g.

Workup

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

Sources & evidence

ORD record
ord-781ea43d94fa4e47a8354a250b2e1b48
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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