1-Hydroxybenzotriazole → 4-((S)-2-{[5-[2-((S)-2-Benzyloxycarbonyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-(3-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-4-tert-butoxycarbonyl-butyryl)-piperazine-1-carboxylic acid ethyl ester

HRID 1970439Notes

Reaction equation

HRID 1970439 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:43])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([O:31][CH2:32][C:33](O)=[O:34])[N:28]([C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[CH:37]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[CH2:64]([O:71][C:72](=[O:78])[C@@H:73]1[CH2:77][CH2:76][CH2:75][NH:74]1)[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1>CN(C=O)C.C(OCC)(=O)C.C(Cl)CCl>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12](=[O:43])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([O:31][CH2:32][C:33]([N:74]3[CH2:75][CH2:76][CH2:77][C@H:73]3[C:72]([O:71][CH2:64][C:65]3[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=3)=[O:78])=[O:34])[N:28]([C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[CH:37]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733413Proline benzyl ester hydrochlorideHCID 668546774-((S)-4-tert-Butoxycarbonyl-2-{[5-carboxymethoxy-1-(3-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl ester

Product 1

HCID 668556844-((S)-2-{[5-[2-((S)-2-Benzyloxycarbonyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-(3-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-4-tert-butoxycarbonyl-butyryl)-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2.000 g 4-((S)-4-tert-Butoxycarbonyl-2-{[5-carboxymethoxy-1-(3-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl ester in 20 ml DMF were added 0.506 g HOBt, 1.2 ml DIPEA and 0.798 g L-proline benzyl ester hydrochloride at RT. Then 0.633 g EDC was added portionwise and the suspension stirred at RT for 12 h. The reaction mixture was diluted with ethyl acetate and subsequently extracted with aqueous LiCl (4% w/w), 0.1 M HCl and aqueous NaHCO3. The organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The crude product thus obtained was used in the subsequent reaction.

Workup

  1. extractionsubsequently extracted with aqueous LiCl (4% w/w), 0.1 M HCl and aqueous NaHCO3
  2. dry with materialThe organic layer was dried over MgSO4
  3. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-2ed43a71835247f796b27a6781238c40
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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