1-Hydroxybenzotriazole → HCID 66856916, compound

HRID 1970444Notes

Reaction equation

HRID 1970444 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:42])[C@@H:13]([NH:22][C:23]([C:25]2[CH:29]=[C:28]([O:30][CH2:31][C:32](O)=[O:33])[N:27]([C:35]3[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=3)[N:26]=2)=[O:24])[CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:8][CH2:7]1)=[O:5])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[CH2:63]([O:70][C:71](=[O:77])[C@@H:72]1[CH2:76][CH2:75][CH2:74][NH:73]1)[C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=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:42])[C@@H:13]([NH:22][C:23]([C:25]2[CH:29]=[C:28]([O:30][CH2:31][C:32]([N:73]3[CH2:74][CH2:75][CH2:76][C@H:72]3[C:71]([O:70][CH2:63][C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=3)=[O:77])=[O:33])[N:27]([C:35]3[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=3)[N:26]=2)=[O:24])[CH2:14][C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733413Proline benzyl ester hydrochlorideHCID 66854684HCID 66854684, compound

Product 1

HCID 66856916HCID 66856916, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2.000 g 4-((S)-3-tert-Butoxycarbonyl-2-{[5-carboxymethoxy-1-(3-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionyl)-piperazine-1-carboxylic acid ethyl ester in 20 ml DMF were added 0.518 g HOBt, 1.2 ml DIPEA and 0.817 g L-proline benzyl ester hydrochloride at RT. Then 0.648 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. Yield: 2.5 g.

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-06b0f48924f64c35a7aace9c891508db
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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