Diisopropylethylamine → 4-[(S)-4-tert-Butoxycarbonyl-2-({5-[2-((S)-4,4-difluoro-2-methoxycarbonyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester

HRID 1970562ノート

反応式

HRID 1970562 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](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=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH3:62][O:63][C:64]([C@@H:66]1[CH2:70][C:69]([F:72])([F:71])[CH2:68][NH:67]1)=[O:65]>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]([N:67]3[CH2:68][C:69]([F:72])([F:71])[CH2:70][C@H:66]3[C:64]([O:63][CH3:62])=[O:65])=[O:34])[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]

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 45082563methyl (2S)-4,4-difluoropyrrolidine-2-carboxylateHCID 46186284HCID 46186284、化合物

生成物 1

HCID 668544804-[(S)-4-tert-Butoxycarbonyl-2-({5-[2-((S)-4,4-difluoro-2-methoxycarbonyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid ethyl ester

試薬・触媒・溶媒 3

HCID 111,2-Dichloroethane溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 1.2 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 278 mg HOAt, 1.6 g EDC, 1.1 ml DIPEA and 684 mg (S)-4,4-Difluoro-pyrrolidine-2-carboxylic acid methyl ester hydrotrifluoroacetate. After 36 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 purified by chromatography on silica using heptan/ethyl acetate 40/60 to 33/67 as eluent.

後処理

  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

出典と根拠

ORDレコード
ord-91b9d79f52424dd1bc6dab44198993f0
出典データセット
uspto-grants-2013_04
特許番号
US08426420B2

反応ノート

読み込み中…