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 1970562노트

반응식

HRID 1970562 반응식
[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]

참가 물질

8

반응물 4

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

생성물 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

시약·촉매·용매 3

HCID 111,2-Dichloroethane용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-91b9d79f52424dd1bc6dab44198993f0
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08426420B2

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