Ethyl Acetate → 4-[(S)-3-tert-Butoxycarbonylamino-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-propionyl]-piperazine-1-carboxylic acid ethyl ester

HRID 1970457Notes

Reaction equation

HRID 1970457 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.CN(C(ON1N=NC2[CH:42]=[CH:43][CH:44]=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:55]CN(C(C)C)C(C)C.[CH2:64]([O:66][C:67]([N:69]1[CH2:74][CH2:73][N:72]([C:75](=[O:87])[C@@H:76]([NH2:86])[CH:77]([NH2:85])C(OC(C)(C)C)=O)[CH2:71][CH2:70]1)=[O:68])[CH3:65].[C:88]([O:91]CC)(=[O:90])C>CN(C=O)C>[CH2:64]([O:66][C:67]([N:69]1[CH2:70][CH2:71][N:72]([C:75](=[O:87])[C@@H:76]([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:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:19]=2)=[O:28])[CH2:77][NH:85][C:88]([O:91][C:43]([CH3:42])([CH3:44])[CH3:55])=[O:90])[CH2:73][CH2:74]1)=[O:68])[CH3:65]

Participants

7

Reactant 5

HCID 8857Ethyl AcetateHCID 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 668550634-((S)-2-amino-3-tert-butoxycarbonyl-amino-propionyl)-piperazine-1-carboxylic acid ethyl ester

Product 1

HCID 668549444-[(S)-3-tert-Butoxycarbonylamino-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-propionyl]-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 390 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 359 mg HATU and 156 μl DIPEA. After 10 minutes a solution of 326 mg 4-((S)-2-amino-3-tert-butoxycarbonyl-amino-propionyl)-piperazine-1-carboxylic acid ethyl ester in 2 ml DMF was added and after 30 minutes the reaction mixture was diluted with ethyl acetate and extracted with aqueous LiCl (4%), 0.1 M HCl and saturated NaHCO3. The crude product (600 mg) thus obtained after evaporation of the solvent was deprotected in the following step.

Workup

  1. extractionextracted with aqueous LiCl (4%), 0.1 M HCl and saturated NaHCO3

Sources & evidence

ORD record
ord-b67ced9594d34b4b88e6bb7b8d17caeb
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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