Trifluoroacetic acid → 4-{(S)-4-Carboxy-2-[(5-{2-[(S)-2-(3-cyclopropyl-[1,2,4]oxadiazol-5-yl)-pyrrolidin-1-yl]-2-oxo-ethoxy}-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester

HRID 1970587ノート

反応式

HRID 1970587 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(C)(C)C)=[O:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2].CN(C([O:50][N:51]1N=N[C:53]2[CH:54]=[CH:55]C=[N:57][C:52]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=NC2N(O)N=NC=2C=1.CC[N:79]([CH:83]([CH3:85])[CH3:84])[CH:80]([CH3:82])C.C(O)(C(F)(F)F)=O>CN(C=O)C.C(Cl)Cl>[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:79]3[CH2:80][CH2:82][CH2:85][C@H:83]3[C:84]3[O:50][N:51]=[C:52]([CH:53]4[CH2:55][CH2:54]4)[N:57]=3)=[O:35])[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]([OH:18])=[O:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2]

参加物

8

反応物 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 46186284HCID 46186284、化合物

生成物 1

HCID 668553354-{(S)-4-Carboxy-2-[(5-{2-[(S)-2-(3-cyclopropyl-[1,2,4]oxadiazol-5-yl)-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 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of 213 mg 4-{(S)-4-tert-Butoxycarbonyl-2-[(5-carboxymethoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester in 7 ml DMF were added 138 mg HATU, 50 mg HOAT, 0.19 ml DIPEA and 65 mg 3-Cyclopropyl-5-(S)-pyrrolidin-2-yl-[1,2,4]oxadiazole. It was concentrated, the residue dissolved in dichloromethane and extracted with aqueous LiCl (4% w/w), aqueous NaHCO3 and 0.1 M HCl. The organic layer was dried over MgSO4 and concentrated to furnish the crude coupling product as colorless oil. The latter one was dissolved in 10 ml DCM and treated with 403 μl TFA. After stirring for 12 h the solvents were removed under reduced pressure and the residue purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA) to give the title compound.

後処理

  1. concentrationIt was concentrated
  2. dissolutionthe residue dissolved in dichloromethane
  3. extractionextracted with aqueous LiCl (4% w/w), aqueous NaHCO3 and 0.1 M HCl
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customto furnish the crude coupling product as colorless oil
  7. customwere removed under reduced pressure
  8. customthe residue purified by preparative HPLC (
  9. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)

出典と根拠

ORDレコード
ord-02e3142dd2654a9db4c450802fd247ef
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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