benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate → HCID 59676141, Verbindung

HRID 1391711Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1391711
[CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:17][C@@H:18]([OH:40])[C@@H:19]([NH:29]C(=O)OCC2C=CC=CC=2)[CH2:20][C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=2)[CH2:6]1)[CH:2]=[CH2:3]>COCCOC.O>[CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:17][C@@H:18]([OH:40])[C@@H:19]([NH2:29])[CH2:20][C:21]2[CH:22]=[C:23]([F:28])[CH:24]=[C:25]([F:27])[CH:26]=2)[CH2:6]1)[CH:2]=[CH2:3]

Komponenten

3

Edukt 1

HCID 59676145benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate

Produkt 1

HCID 59676141HCID 59676141, VerbindungAusbeute 38 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 18180031Water 1,2-dimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

Step E (2): Ba(OH)2.H2O (267 mg, 1.41 mmol) was added to a vial charged with benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate (diastereomer A, 260 mg, 0.471 mmol) from stepE(1), DME/H2O (3 mL/2 mL). The sealed vial was heated at 110° C. for 18 h. Filtered the reaction mixture through a Pasture pipette/Kimwipe plug to remove solids. Rinsed the vessel and solids with fresh DME. The filtrate was evaporated in vacuo. Residual solvents were removed under high vacuum. The crude residue was purified by silica gel chromatography (1-20% MeOH (containing 0.1% triethylamine)/chloroform linear gradient) to give 74 mg (38% yield) the of the title compound as a clear viscous oil. LC-MS (M+H)+=419.24; 1H NMR (500 MHz, CDCl3) δ 7.32 (d, J=8.24 Hz, 1H), 6.92 (d, J=2.14 Hz, 1H), 6.85 (dd, J=8.24, 2.44 Hz, 1H), 6.71-6.80 (m, 2H), 6.60-6.71 (m, 1H), 5.84-6.03 (m, 1H), 5.30 (dd, J=17.24, 1.68 Hz, 1H), 5.18 (dd, J=10.38, 1.53 Hz, 1H), 4.77 (dd, J=6.10, 3.97 Hz, 1H), 4.08-4.12 (m, 2H), 4.05 (dd, J=6.87, 4.43 Hz, 1H), 3.79 (s, 3H), 3.47-3.52 (m, 1H), 3.04-3.10 (m, 1H), 2.90-3.00 (m, 2H), 2.75 (dd, J=11.90, 8.55 Hz, 1H), 2.61-2.68 (m, 1H), 2.49 (dd, J=13.43, 9.77 Hz, 1H), 1.94-2.00 (m, 1H).

Aufarbeitung

  1. filtrationFiltered the reaction mixture through a Pasture pipette/Kimwipe plug
  2. customto remove solids
  3. washRinsed the vessel and solids with fresh DME
  4. customThe filtrate was evaporated in vacuo
  5. customResidual solvents were removed under high vacuum
  6. customThe crude residue was purified by silica gel chromatography (1-20% MeOH (containing 0.1% triethylamine)/chloroform linear gradient)

Quellen und Nachweise

ORD-Eintrag
ord-693111dae74a40908959414ba0dac6fc
Quelldatensatz
uspto-grants-2008_03
Patentnummer
US07338974B2

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