1,2-Dichloroethane → 1-9H-fluoren-9-ylmethyl (2R,3S)-4-(3,5-difluorophenyl)-2-hydroxy-3-{[5-oxo-5-(1-piperidinyl)pentanoyl]amino}butyl(3-iodobenzyl)carbamate

HRID 857260Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 857260
[CH:1]1[CH:2]=[CH:3][C:4]2N(O)N=[N:7][C:5]=2C=1.[CH2:11](Cl)[CH2:12]Cl.Cl.[NH2:16][C@@H:17]([CH2:47][C:48]1[CH:53]=[C:52]([F:54])[CH:51]=[C:50]([F:55])[CH:49]=1)[C@H:18]([OH:46])[CH2:19][N:20]([CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([I:45])[CH:40]=1)[C:21](=[O:37])[O:22][CH2:23][CH:24]1[C:36]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:30]2[C:25]1=[CH:26][CH:27]=[CH:28][CH:29]=2.CN1[CH2:62][CH2:61][O:60]CC1.CN([CH:66]=[O:67])C>>[F:55][C:50]1[CH:49]=[C:48]([CH2:47][C@H:17]([NH:16][C:61](=[O:60])[CH2:62][CH2:11][CH2:12][C:66](=[O:67])[N:7]2[CH2:1][CH2:2][CH2:3][CH2:4][CH2:5]2)[C@H:18]([OH:46])[CH2:19][N:20]([CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([I:45])[CH:40]=2)[C:21](=[O:37])[O:22][CH2:23][CH:24]2[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:30]=3[C:31]3[C:36]2=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:53]=[C:52]([F:54])[CH:51]=1

Komponenten

6

Edukt 5

HCID 111,2-DichloroethaneHCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 865858561-9H-fluoren-9-ylmethyl(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl(3-iodobenzyl)carbamate hydrochloride

Produkt 1

HCID 587598521-9H-fluoren-9-ylmethyl (2R,3S)-4-(3,5-difluorophenyl)-2-hydroxy-3-{[5-oxo-5-(1-piperidinyl)pentanoyl]amino}butyl(3-iodobenzyl)carbamate

Versuchsvorschrift

HOBt (81 mg, 0.6 mmole) and EDC (105 mg, 0.55 mmole) are added to 1-carboxy-5-piperdinylglutaramide (IX, 100 mg, 0.5 mmole) in DMF (2 ml). The acid is activated 60 minutes then treated with 1-9H-fluoren-9-ylmethyl (2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl(3-iodobenzyl)carbamate hydrochloride (XXXV, PREPARATION 14, 300 mg, 0.43 mmole) and NMM (0.19 ml, 1.72 mmole). The reaction is stirred 3 hrs then concentrated under reduced pressure. The residue is partitioned between ethyl acetate and saturated aqueous bicarbonate. The organic phases are washed with aqueous potassium bisulfate, saline, dried over sodium sulfate and finally concentrated under reduced pressure to give crude product. Purification via flash chromatography with ethyl acetate/hexane (50/50) then methanol/ethyl acetate (10/90) gives the title compound, M+H=838 g/m.

Aufarbeitung

  1. concentrationthen concentrated under reduced pressure
  2. customThe residue is partitioned between ethyl acetate and saturated aqueous bicarbonate
  3. washThe organic phases are washed with aqueous potassium bisulfate, saline
  4. dry with materialdried over sodium sulfate
  5. concentrationfinally concentrated under reduced pressure
  6. customto give crude product
  7. customPurification via flash chromatography with ethyl acetate/hexane (50/50)

Quellen und Nachweise

ORD-Eintrag
ord-4544216b03f244b4977fb1faa597af61
Quelldatensatz
uspto-grants-2006_12
Patentnummer
US07144897B2

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