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

HRID 1970422ノート

反応式

HRID 1970422 の反応式
[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]([OH:35])=O)[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.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(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]([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:35])[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]([CH3:21])([CH3:22])[CH3:20])=[O:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2]

参加物

7

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733413Proline benzyl ester hydrochlorideHCID 46186284HCID 46186284、化合物

生成物 1

HCID 461862854-[(S)-2-({5-[2-((S)-2-Benzyloxycarbonyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-4-tert-butoxycarbonyl-butyryl]-piperazine-1-carboxylic acid ethyl ester

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 9.5 g 4-{(S)-4-tert-Butoxycarbonyl-2-[(5-carboxymethoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester in 80 ml DMF were added 2.5 g HOBt, 5.7 ml DIPEA and 3.9 g L-proline benzyl ester hydrochloride at 0° C. At this temperature were added 3.1 g EDC portionwise and the suspension allowed to warm to RT over a period of 12 h. The solvent was evaporated, the residue dissolved in 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.

後処理

  1. customThe solvent was evaporated
  2. dissolutionthe residue dissolved in ethyl acetate
  3. extractionsubsequently extracted with aqueous LiCl (4 w/w), 0.1 M HCl and aqueous NaHCO3
  4. dry with materialThe organic layer was dried over MgSO4
  5. customthe solvent was removed under reduced pressure

出典と根拠

ORDレコード
ord-793fb56ceb5547c3ab4de0f612f6091e
出典データセット
uspto-grants-2013_04
特許番号
US08426420B2

反応ノート

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