Diethylethanolamine → (s)-2-((s)-3-Acetamido-3-((r)-sec-butyl)-2-oxopyrrolidin-1-yl)-n-((1r,2s)-1-hydroxy-3-phenyl-1-((2r,4r)-4-(propylsulfonyl)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

HRID 132970

Reaktionsgleichung

Reaktionsgleichung von HRID 132970
[C:1]([NH:4][C@:5]1([C@@H:58]([CH2:60][CH3:61])[CH3:59])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:49][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[C:11]([NH:13][C@@H:14]([CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C@@H:15]([C@H:24]2[CH2:28][C@@H:27]([S:29]([CH2:32][CH2:33][CH3:34])(=[O:31])=[O:30])[CH2:26][N:25]2C(OC(C)(C)C)=O)[O:16][Si](C(C)(C)C)(C)C)=[O:12])[C:6]1=[O:57])(=[O:3])[CH3:2].CCN(CCO)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[C:1]([NH:4][C@:5]1([C@@H:58]([CH2:60][CH3:61])[CH3:59])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:49][CH2:50][C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)[C:11]([NH:13][C@@H:14]([CH2:42][C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[C@H:15]([OH:16])[C@H:24]2[CH2:28][C@@H:27]([S:29]([CH2:32][CH2:33][CH3:34])(=[O:30])=[O:31])[CH2:26][NH:25]2)=[O:12])[C:6]1=[O:57])(=[O:3])[CH3:2]

Komponenten

5

Edukt 3

HCID 7497DiethylethanolamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69197054(2r,4r)-Tert-butyl 2-((1s,2s)-2-((s)-2-((s)-3-acetamido-3-((r)-sec-butyl)-2-oxopyrrolidin-1-yl)-4-phenylbutanamido)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylate

Produkt 1

HCID 69195114(s)-2-((s)-3-Acetamido-3-((r)-sec-butyl)-2-oxopyrrolidin-1-yl)-n-((1r,2s)-1-hydroxy-3-phenyl-1-((2r,4r)-4-(propylsulfonyl)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamideAusbeute 85 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Step 22 (F): (2R,4R)-tert-butyl 2-((1S,2S)-2-((S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-4-phenylbutanamido)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylate. A solution of the compound of Preparation A (22 mg, 0.06 mmol) dissolved in 2 mL of dichloromethane was treated with DEEA (40 mg, 0.3 mmol) and HATU (30 mg, 0.078 mmol). After stirring at rt for 5 min, the amine from step 22 (E) (32 mg, 0.06 mmol) was added and the reaction solution was allowed to stir for 16 h at rt. The reaction solution was then partitioned between ethyl acetate and water, the organic layer was concentrated, and the crude product was purified by chromatography eluting with a gradient of 40% to 80% ethyl acetate in hexanes to provide 45 mg (85%) of the desired amide. 1H NMR (500 MHz, Solvent) δ ppm 0.08 (s, 6 H) 0.18 (s, 2 H) 0.73 (d, J=6.71 Hz, 3 H) 0.99 (s, 9 H) 1.10 (m, 6 H) 1.37 (t, J=6.41 Hz, 6 H) 1.49 (s, 9 H) 1.52 (d, J=3.97 Hz, 4 H) 1.68 (m, 1 H) 1.86 (m, 2 H) 2.09 (m, 1 H) 2.58 (m, 1 H) 2.73 (m, 1 H) 3.05 (dd, J=9.16, 6.41 Hz, 2 H) 3.23 (m, 2 H) 3.54 (s, 1 H) 3.76 (m, 2 H) 4.02 (m, 2 H) 4.09 (m, 1 H) 4.26 (s, 1 H) 4.41 (d, J=8.55 Hz, 1 H) 7.22 (m, 10 H) 8.18 (s, 1 H). MS (ESI) (M+H)+=883.41

Aufarbeitung

  1. customA solution of the compound of Preparation A (22 mg, 0.06 mmol)
  2. stirringto stir for 16 h at rt
  3. customThe reaction solution was then partitioned between ethyl acetate and water
  4. concentrationthe organic layer was concentrated
  5. customthe crude product was purified by chromatography
  6. washeluting with a gradient of 40% to 80% ethyl acetate in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-17382c3185214860ba1a5a76715e361a
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07388007B2

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