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

HRID 1908653Notes

Reaction equation

HRID 1908653 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: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]=[CH:38][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.[CH2:62]([O:69][C:70]([C:72]1([NH2:76])[CH2:75][CH2:74][CH2:73]1)=[O:71])[C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1>CN(C=O)C.C(OCC)(=O)C.C(Cl)CCl>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:42])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([O:31][CH2:32][C:33](=[O:34])[NH:76][C:72]3([C:70]([O:69][CH2:62][C:63]4[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=4)=[O:71])[CH2:73][CH2:74][CH2:75]3)[N:28]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=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]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 22120948Benzyl 1-aminocyclobutane-1-carboxylateHCID 46186284HCID 46186284, compound

Product 1

HCID 669201834-[(S)-2-({5-[(1-Benzyloxycarbonyl-cyclobutylcarbamoyl)-methoxy]-1-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 4.9 g 4-{(S)-4-tert-butoxycarbonyl-2-[(5-carboxymethoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester in 35 ml DMF were added 1.3 g HOBt, 1.6 g EDC, 2.7 ml DIPEA and 1.7 g 1-Amino-cyclobutanecarboxylic acid benzyl ester. After 12 h the mixture was diluted with ethyl acetate and subsequently extracted with aqueous LiCl (4% w/w), 0.1 M HCl and saturated 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: 4.7 g

Workup

  1. extractionsubsequently extracted with aqueous LiCl (4% w/w), 0.1 M HCl and saturated 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-353aae1279224900a5b9948c63bb8210
Source dataset
uspto-grants-2013_12
Patent number
US08598179B2

Reaction notes

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