Diisopropylethylamine → 4-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-4-(2H-tetrazol-5-yl)-butyryl]-piperazine-1-carboxylic acid butyl ester

HRID 1970518Notes

Reaction equation

HRID 1970518 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]([OH:29])=O)[CH:17]=2)=[O:7])[CH2:4][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.[CH2:64]([O:68][C:69]([N:71]1[CH2:76][CH2:75][N:74]([C:77](=[O:87])[C@@H:78]([NH2:86])[CH2:79][CH2:80][C:81]2[N:82]=[N:83][NH:84][N:85]=2)[CH2:73][CH2:72]1)=[O:70])[CH2:65][CH2:66][CH3:67]>CN(C=O)C>[CH2:64]([O:68][C:69]([N:71]1[CH2:72][CH2:73][N:74]([C:77](=[O:87])[C@@H:78]([NH:86][C:27]([C:18]2[CH:17]=[C:16]([O:15][CH2:14][C:13]([N:9]3[CH2:10][CH2:11][CH2:12][C@H:8]3[C:6](=[O:7])[NH:5][CH:1]3[CH2:4][CH2:3][CH2:2]3)=[O:30])[N:20]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:19]=2)=[O:29])[CH2:79][CH2:80][C:81]2[N:85]=[N:84][NH:83][N:82]=2)[CH2:75][CH2:76]1)=[O:70])[CH2:65][CH2:66][CH3:67]

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 668546955-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acidHCID 668553394-[(S)-2-Amino-4-(2H-tetrazol-5-yl)-butyryl]-piperazine-1-carboxylic acid butyl ester

Product 1

HCID 441291374-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-4-(2H-tetrazol-5-yl)-butyryl]-piperazine-1-carboxylic acid butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 327 mg 5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid in 5 ml DMF were added 415 μl DIPEA, 302 mg HATU and 360 mg 4-[(S)-2-amino-4-(2H-tetrazol-5-yl)-butyryl]-piperazine-1-carboxylic acid butyl ester hydrotrifluoroacetate. After 30 minutes the reaction mixture was concentrated and the crude product obtained 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: 180 mg

Workup

  1. concentrationAfter 30 minutes the reaction mixture was concentrated

Sources & evidence

ORD record
ord-4b0471e7a31a4c248b7edad02bdcfe98
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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